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</svg> Books</a></div><div class="jr-rhead f1 flexh"><div class="head"></div><div class="body"><div class="t">Mistletoe Extracts (PDQ®): Health Professional Version</div><div class="j">PDQ Cancer Information Summaries [Internet]</div></div><div class="tail"></div></div><div id="jr-tb2"><a id="jr-bkhelp-sw" class="btn wsprkl hidden" title="Help with NLM PubReader">?</a><a id="jr-help-sw" class="btn wsprkl hidden" title="Settings and typography in NLM PubReader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512" preserveAspectRatio="none"><path d="M462,283.742v-55.485l-29.981-10.662c-11.431-4.065-20.628-12.794-25.274-24.001 c-0.002-0.004-0.004-0.009-0.006-0.013c-4.659-11.235-4.333-23.918,0.889-34.903l13.653-28.724l-39.234-39.234l-28.72,13.652 c-10.979,5.219-23.68,5.546-34.908,0.889c-0.005-0.002-0.01-0.003-0.014-0.005c-11.215-4.65-19.933-13.834-24-25.273L283.741,50 h-55.484l-10.662,29.981c-4.065,11.431-12.794,20.627-24.001,25.274c-0.005,0.002-0.009,0.004-0.014,0.005 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class="title" itemprop="name">Mistletoe Extracts (PDQ®)</span></h1><div class="subtitle whole_rhythm">Health Professional Version</div><p class="contribs">PDQ Integrative, Alternative, and Complementary Therapies Editorial Board.</p><p class="fm-aai"><a href="#_NBK66054_pubdet_">Publication Details</a></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="_abs_rndgid_" itemprop="description"><p id="CDR0000269596__243">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of mistletoe extracts in the treatment of people with cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.</p><p id="CDR0000269596__244">This summary is reviewed regularly and updated as necessary by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p></div><div id="CDR0000269596__1"><h2 id="_CDR0000269596__1_">Overview</h2><p id="CDR0000269596__2">This <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045333/" class="def">cancer</a> information summary provides an overview of the use of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285939/" class="def">mistletoe</a> as a treatment for people with cancer. The summary includes a brief history of mistletoe research, the results of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045961/" class="def">clinical trials</a>, and possible <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046580/" class="def">side effects</a> of mistletoe use.</p><p id="CDR0000269596__3">This summary contains the following key information:</p><ul id="CDR0000269596__4"><li class="half_rhythm"><div>Mistletoe is a <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044075/" class="def">semiparasitic</a> plant that has been used for centuries to treat numerous human ailments.</div></li><li class="half_rhythm"><div>Mistletoe is used commonly in Europe, where a variety of different extracts are manufactured and marketed as <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044678/" class="def">injectable</a> prescription drugs. These injectable drugs are not available commercially in the United States and are not approved as a treatment for people with cancer.</div></li><li class="half_rhythm"><div>Mistletoe is one of the most widely studied CAM therapies for cancer. In certain European countries, the preparations made from European mistletoe (<i>Viscum album</i>, Loranthaceae) are among the most prescribed drugs offered to cancer patients.</div></li><li class="half_rhythm"><div>Although mistletoe plants and berries are considered poisonous to humans, few serious side effects have been associated with mistletoe extract use. </div></li><li class="half_rhythm"><div>
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The use of mistletoe as a treatment for people with cancer has been investigated in <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044195/" class="def">clinical studies</a>. Reports of improved survival and/or <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045417/" class="def">quality of life</a> have been common, but many of the studies had major weaknesses that raise doubts about the reliability of the findings.</div></li><li class="half_rhythm"><div>At present, the use of mistletoe cannot be recommended outside the context of well-designed clinical trials. Such trials will be valuable to determine more clearly whether mistletoe can be useful in the treatment of specific subsets of cancer patients.</div></li></ul><p id="CDR0000269596__5">Many of the medical and scientific terms used in this summary are hypertext linked (at first use in each section) to the <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI Dictionary of Cancer Terms</a>, which is oriented toward nonexperts. When a linked term is clicked, a definition will appear in a separate window. </p><p id="CDR0000269596__6">Reference citations in some <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044271/" class="def">PDQ</a> cancer information summaries may include links to external websites that are operated by individuals or organizations for the purpose of marketing or advocating the use of specific treatments or products. These reference citations are included for informational purposes only. Their inclusion should not be viewed as an endorsement of the content of the websites, or of any treatment or product, by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board or the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044266/" class="def">National Cancer Institute</a>.</p></div><div id="CDR0000269596__7"><h2 id="_CDR0000269596__7_">General Information</h2><p id="CDR0000269596__9"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285939/" class="def">Mistletoe</a>, a <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044075/" class="def">semiparasitic</a> plant, holds interest as a potential anticancer agent because <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000407760/" class="def">extracts</a> derived from it have been shown to kill <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045333/" class="def">cancer</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046476/" class="def">cells</a>
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<i><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045733/" class="def">in vitro</a></i>
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[<a class="bibr" href="#CDR0000269596_rl_7_1" rid="CDR0000269596_rl_7_1">1</a>-<a class="bibr" href="#CDR0000269596_rl_7_10" rid="CDR0000269596_rl_7_10">10</a>] to down-regulate central <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000045693/" class="def">genes</a> involved in tumor progression, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045771/" class="def">malignancy</a>, and cell migration and invasion, such as TGF-beta and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044211/" class="def">matrix-metalloproteinases</a>.[<a class="bibr" href="#CDR0000269596_rl_7_11" rid="CDR0000269596_rl_7_11">11</a>,<a class="bibr" href="#CDR0000269596_rl_7_12" rid="CDR0000269596_rl_7_12">12</a>]
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Mistletoe extracts have been shown to do the following:[<a class="bibr" href="#CDR0000269596_rl_7_10" rid="CDR0000269596_rl_7_10">10</a>-<a class="bibr" href="#CDR0000269596_rl_7_31" rid="CDR0000269596_rl_7_31">31</a>] </p><ul id="CDR0000269596__273"><li class="half_rhythm"><div>Enforce <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044062/" class="def">natural killer cell</a>-mediated <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046634/" class="def">tumor</a> cell <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044606/" class="def">lysis</a>.</div></li><li class="half_rhythm"><div>Reduce the migratory and invasive potential of tumor cells.</div></li><li class="half_rhythm"><div>Stimulate <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046356/" class="def">immune system</a> cells both <i>in vitro</i> and <i><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046352/" class="def">in vivo</a></i>.</div></li></ul><p id="CDR0000269596__274">Three components of mistletoe, namely <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044094/" class="def">viscotoxins</a>, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044162/" class="def">polysaccharides</a>, and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044051/" class="def">lectins</a>, may be responsible for these effects.[<a class="bibr" href="#CDR0000269596_rl_7_10" rid="CDR0000269596_rl_7_10">10</a>,<a class="bibr" href="#CDR0000269596_rl_7_13" rid="CDR0000269596_rl_7_13">13</a>-<a class="bibr" href="#CDR0000269596_rl_7_15" rid="CDR0000269596_rl_7_15">15</a>,<a class="bibr" href="#CDR0000269596_rl_7_19" rid="CDR0000269596_rl_7_19">19</a>-<a class="bibr" href="#CDR0000269596_rl_7_21" rid="CDR0000269596_rl_7_21">21</a>,<a class="bibr" href="#CDR0000269596_rl_7_23" rid="CDR0000269596_rl_7_23">23</a>-<a class="bibr" href="#CDR0000269596_rl_7_25" rid="CDR0000269596_rl_7_25">25</a>,<a class="bibr" href="#CDR0000269596_rl_7_32" rid="CDR0000269596_rl_7_32">32</a>-<a class="bibr" href="#CDR0000269596_rl_7_39" rid="CDR0000269596_rl_7_39">39</a>] Viscotoxins are small <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046092/" class="def">proteins</a> that exhibit cell-killing activity and possible immune system–stimulating activity.[<a class="bibr" href="#CDR0000269596_rl_7_1" rid="CDR0000269596_rl_7_1">1</a>,<a class="bibr" href="#CDR0000269596_rl_7_6" rid="CDR0000269596_rl_7_6">6</a>,<a class="bibr" href="#CDR0000269596_rl_7_20" rid="CDR0000269596_rl_7_20">20</a>,<a class="bibr" href="#CDR0000269596_rl_7_21" rid="CDR0000269596_rl_7_21">21</a>,<a class="bibr" href="#CDR0000269596_rl_7_40" rid="CDR0000269596_rl_7_40">40</a>,<a class="bibr" href="#CDR0000269596_rl_7_41" rid="CDR0000269596_rl_7_41">41</a>] Lectins are complex <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045065/" class="def">molecules</a> made of both protein and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285960/" class="def">carbohydrates</a> that are capable of binding to the outside of cells (e.g., immune system cells) and inducing biochemical changes in them.[<a class="bibr" href="#CDR0000269596_rl_7_10" rid="CDR0000269596_rl_7_10">10</a>,<a class="bibr" href="#CDR0000269596_rl_7_42" rid="CDR0000269596_rl_7_42">42</a>-
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<a class="bibr" href="#CDR0000269596_rl_7_45" rid="CDR0000269596_rl_7_45">45</a>]</p><p id="CDR0000269596__275">In view of mistletoe’s ability to stimulate the immune system, it has been classified as a type of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045616/" class="def">biological response modifier</a>.[<a class="bibr" href="#CDR0000269596_rl_7_42" rid="CDR0000269596_rl_7_42">42</a>] Biological response modifiers constitute a diverse group of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044510/" class="def">biological</a> molecules that have been used individually, or in combination with other agents, to treat cancer or to lessen the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046580/" class="def">side effects</a> of anticancer drugs. Mistletoe extracts have been demonstrated in preclinical settings to have other mechanisms of action, such as antiangiogenesis.[<a class="bibr" href="#CDR0000269596_rl_7_29" rid="CDR0000269596_rl_7_29">29</a>]</p><p id="CDR0000269596__10">Preparations from mistletoe extracts are most frequently used in the treatment of cancer patients in German-speaking countries.[<a class="bibr" href="#CDR0000269596_rl_7_46" rid="CDR0000269596_rl_7_46">46</a>] Commercially available extracts are marketed under a variety of brand names, including Iscador (see explanation of suffixes below), Eurixor, Helixor, Isorel, Iscucin, Plenosol, and abnobaVISCUM. Some extracts are marketed under more than one name. Iscador, Isorel, and Plenosol are also sold as Iscar, Vysorel, and Lektinol, respectively. All of these products are prepared from <i>Viscum album</i> (Loranthaceae) (<i>Viscum album</i> L. or European mistletoe). They are not sold as a drug in the United States. Eurixor, Isorel, and Vysorel are no longer commercially available.</p><p id="CDR0000269596__100">In addition to European mistletoe, extracts from a type of Korean mistletoe (<i>Viscum album </i>var. <i>coloratum</i> [Kom.] Ohwi) have demonstrated <i>in vitro</i> and <i>in vivo</i> cytotoxicity in laboratory studies.[<a class="bibr" href="#CDR0000269596_rl_7_47" rid="CDR0000269596_rl_7_47">47</a>-<a class="bibr" href="#CDR0000269596_rl_7_51" rid="CDR0000269596_rl_7_51">51</a>]</p><p id="CDR0000269596__11">Mistletoe grows on several types of trees, and the chemical composition of extracts derived from it depends on the following:[<a class="bibr" href="#CDR0000269596_rl_7_8" rid="CDR0000269596_rl_7_8">8</a>,<a class="bibr" href="#CDR0000269596_rl_7_43" rid="CDR0000269596_rl_7_43">43</a>,<a class="bibr" href="#CDR0000269596_rl_7_52" rid="CDR0000269596_rl_7_52">52</a>-<a class="bibr" href="#CDR0000269596_rl_7_55" rid="CDR0000269596_rl_7_55">55</a>]</p><ul id="CDR0000269596__276"><li class="half_rhythm"><div> Species of the host tree (e.g., apple, elm, oak, pine, poplar, and spruce).</div></li><li class="half_rhythm"><div>Time of year harvested.</div></li><li class="half_rhythm"><div>How the extracts are prepared.</div></li><li class="half_rhythm"><div>The commercial producer.</div></li></ul><p id="CDR0000269596__12">Mistletoe extracts are prepared as <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000043998/" class="def">aqueous</a> solutions or solutions of water and alcohol, and they can be fermented or unfermented.[<a class="bibr" href="#CDR0000269596_rl_7_4" rid="CDR0000269596_rl_7_4">4</a>,<a class="bibr" href="#CDR0000269596_rl_7_6" rid="CDR0000269596_rl_7_6">6</a>,<a class="bibr" href="#CDR0000269596_rl_7_22" rid="CDR0000269596_rl_7_22">22</a>,<a class="bibr" href="#CDR0000269596_rl_7_52" rid="CDR0000269596_rl_7_52">52</a>,<a class="bibr" href="#CDR0000269596_rl_7_53" rid="CDR0000269596_rl_7_53">53</a>,<a class="bibr" href="#CDR0000269596_rl_7_56" rid="CDR0000269596_rl_7_56">56</a>-<a class="bibr" href="#CDR0000269596_rl_7_59" rid="CDR0000269596_rl_7_59">59</a>] Some extracts are prepared according to <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045712/" class="def">homeopathic</a> principles, and others are not. Accordingly, as homeopathic preparations, they are typically not chemically standardized extracts.[<a class="bibr" href="#CDR0000269596_rl_7_10" rid="CDR0000269596_rl_7_10">10</a> ,<a class="bibr" href="#CDR0000269596_rl_7_60" rid="CDR0000269596_rl_7_60">60</a>] In addition, the commercial products can be subdivided according to the species of host tree, which is typically indicated in the product name by a suffix letter. Iscador, a fermented aqueous extract of <i>Viscum album</i> L. that is prepared as a homeopathic drug, is marketed as one of the following:[<a class="bibr" href="#CDR0000269596_rl_7_57" rid="CDR0000269596_rl_7_57">57</a>] </p><ul id="CDR0000269596__277"><li class="half_rhythm"><div>IscadorM (from apple trees; <i>Malus domestica</i>).</div></li><li class="half_rhythm"><div>IscadorP (from pine trees; <i>Pinus sylvestris</i>).</div></li><li class="half_rhythm"><div>IscadorQu (from oak trees; <i>Quercus robur</i>).</div></li><li class="half_rhythm"><div>IscadorU (from elm trees; <i>Ulmus minor</i>).</div></li></ul><p id="CDR0000269596__278">Helixor, an unfermented aqueous extract of <i>Viscum album</i> L. that is standardized by its biological effect on human <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045343/" class="def">leukemia</a> cells <i>in vitro</i>, is marketed as one of the following:[<a class="bibr" href="#CDR0000269596_rl_7_57" rid="CDR0000269596_rl_7_57">57</a>]</p><ul id="CDR0000269596__279"><li class="half_rhythm"><div>HelixorA (from spruce trees; <i>Picea abies</i>).</div></li><li class="half_rhythm"><div>HelixorM (from apple trees).</div></li><li class="half_rhythm"><div>HelixorP (from pine trees; <i>Pinus sylvestris</i>).</div></li></ul><p id="CDR0000269596__280">Eurixor (which is no longer commercially available), an unfermented aqueous extract of <i>Viscum album</i> L. harvested from poplar trees, is reportedly standardized to contain a specific amount of one of mistletoe’s lectins (i.e., the lectin ML-1).[<a class="bibr" href="#CDR0000269596_rl_7_57" rid="CDR0000269596_rl_7_57">57</a>] For more information, see the <a href="#CDR0000269596__17">History</a> section. Some proponents contend the choice of extract should depend on the type of tumor and the sex of the patient.[<a class="bibr" href="#CDR0000269596_rl_7_55" rid="CDR0000269596_rl_7_55">55</a>,<a class="bibr" href="#CDR0000269596_rl_7_57" rid="CDR0000269596_rl_7_57">57</a>,<a class="bibr" href="#CDR0000269596_rl_7_61" rid="CDR0000269596_rl_7_61">61</a>,<a class="bibr" href="#CDR0000269596_rl_7_62" rid="CDR0000269596_rl_7_62">62</a>]</p><p id="CDR0000269596__101">A recombinant ML-1 from <i>Escherichia coli</i> bacteria known as rViscumin or aviscumine has been studied in the laboratory and in phase I clinical trials. Because this is not an extract of mistletoe, it is out of the purview of this summary.[<a class="bibr" href="#CDR0000269596_rl_7_63" rid="CDR0000269596_rl_7_63">63</a>]</p><p id="CDR0000269596__13">Mistletoe extracts are usually given by <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045914/" class="def">subcutaneous</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044678/" class="def">injection</a>, although administration by other routes (i.e., <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044068/" class="def">oral</a>, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285972/" class="def">intrapleural</a>, intratumoral, and intravenous) has been described.[<a class="bibr" href="#CDR0000269596_rl_7_19" rid="CDR0000269596_rl_7_19">19</a>,<a class="bibr" href="#CDR0000269596_rl_7_22" rid="CDR0000269596_rl_7_22">22</a>-<a class="bibr" href="#CDR0000269596_rl_7_26" rid="CDR0000269596_rl_7_26">26</a>,<a class="bibr" href="#CDR0000269596_rl_7_39" rid="CDR0000269596_rl_7_39">39</a>,<a class="bibr" href="#CDR0000269596_rl_7_43" rid="CDR0000269596_rl_7_43">43</a>,<a class="bibr" href="#CDR0000269596_rl_7_55" rid="CDR0000269596_rl_7_55">55</a>,<a class="bibr" href="#CDR0000269596_rl_7_57" rid="CDR0000269596_rl_7_57">57</a>,<a class="bibr" href="#CDR0000269596_rl_7_60" rid="CDR0000269596_rl_7_60">60</a>,<a class="bibr" href="#CDR0000269596_rl_7_64" rid="CDR0000269596_rl_7_64">64</a>-<a class="bibr" href="#CDR0000269596_rl_7_70" rid="CDR0000269596_rl_7_70">70</a>] In most reported studies, subcutaneous injections were given 2 to 3 times a week, but the overall duration of treatment varied considerably.</p><p id="CDR0000269596__14"><i>Viscum album</i> is listed in the Homeopathic Pharmacopoeia of the United States, which is the officially recognized compendium for homeopathic drugs in this country.[<a class="bibr" href="#CDR0000269596_rl_7_71" rid="CDR0000269596_rl_7_71">71</a>] Although the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000454785/" class="def">U.S. Food and Drug Administration</a> (FDA) has regulatory authority over homeopathic drugs, this authority is usually not exercised unless the drugs are formulated for injection, such as the mistletoe product described in this summary.</p><p id="CDR0000269596__16">In this summary, the mistletoe extract or product used in each study will be specified wherever possible.</p><div id="CDR0000269596_rl_7"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000269596_rl_7_1">Jung ML, Baudino S, Ribéreau-Gayon G, et al.: Characterization of cytotoxic proteins from mistletoe (Viscum album L.). Cancer Lett 51 (2): 103-8, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2344587" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2344587</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_7_2">Kuttan G, Vasudevan DM, Kuttan R: Effect of a preparation from Viscum album on tumor development in vitro and in mice. J Ethnopharmacol 29 (1): 35-41, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2345458" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2345458</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_7_3">Walzel H, Jonas L, Rosin T, et al.: Relationship between internalization kinetics and cytotoxicity of mistletoe lectin I to L1210 leukaemia cells. Folia Biol (Praha) 36 (3-4): 181-8, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2257937" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2257937</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_7_4">Janssen O, Scheffler A, Kabelitz D: In vitro effects of mistletoe extracts and mistletoe lectins. Cytotoxicity towards tumor cells due to the induction of programmed cell death (apoptosis). Arzneimittelforschung 43 (11): 1221-7, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8292069" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8292069</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_7_5">Jurin M, Zarković N, Hrzenjak M, et al.: Antitumorous and immunomodulatory effects of the Viscum album L. preparation Isorel. Oncology 50 (6): 393-8, 1993 Nov-Dec. 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[<a href="https://pubmed.ncbi.nlm.nih.gov/11279798" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11279798</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_7_60">Mellor D: Mistletoe in homoeopathic cancer treatment. Prof Nurse 4 (12): 605-7, 1989. [<a href="https://pubmed.ncbi.nlm.nih.gov/2813459" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2813459</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_7_61">Fellmer KE: A clinical trial of Iscador: follow-up treatment of irradiated genital carcinomata for the prevention of recurrences. Br Homeopath J 57: 43-7, 1968.</div></li><li><div class="bk_ref" id="CDR0000269596_rl_7_62">Kjaer M: Mistletoe (Iscador) therapy in stage IV renal adenocarcinoma. A phase II study in patients with measurable lung metastases. Acta Oncol 28 (4): 489-94, 1989. [<a href="https://pubmed.ncbi.nlm.nih.gov/2477047" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2477047</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_7_63">Schöffski P, Riggert S, Fumoleau P, et al.: Phase I trial of intravenous aviscumine (rViscumin) in patients with solid tumors: a study of the European Organization for Research and Treatment of Cancer New Drug Development Group. Ann Oncol 15 (12): 1816-24, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15550588" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15550588</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_7_64">Matthes HF, Schad F, Buchwald D, et al.: Endoscopic ultrasound-guided fine-needle Injection of Viscum album L. (mistletoe; Helixor M) in the therapy of primary inoperable pancreas cancer: a pilot study. [Abstract] Gastroenterology 128 (Suppl 2): A-T988, A433-A434, 2005.</div></li><li><div class="bk_ref" id="CDR0000269596_rl_7_65">Matthes HF, Schad F, Schenk G: Viscum album in the therapy of primary inoperable hepatocellular carcinoma (HCC). [Abstract] Gastroenterology 126 (Suppl 2): A-755, A101-A102, 2004.</div></li><li><div class="bk_ref" id="CDR0000269596_rl_7_66">Schaefermeyer G, Schaefermeyer H: Treatment of pancreatic cancer with Viscum album (Iscador): a retrospective study of 292 patients 1986-1996. Complement Ther Med 6 (4): 172-7, 1998.</div></li><li><div class="bk_ref" id="CDR0000269596_rl_7_67">Kleeberg UR, Brocker EB, Lejeune F, et al.: Adjuvant trial in melanoma patients comparing rlFN-alpha to rlFN-gamma to Iscador to a control group after curative resection of high risk primary (>=3mm) or regional lymphnode metastasis (EORTC 18871). [Abstract] Eur J Cancer 35 (Suppl 4): A-264, s82, 1999.</div></li><li><div class="bk_ref" id="CDR0000269596_rl_7_68">Heiny BM, Albrecht V, Beuth J: Stabilization of quality of life with mistletoe lectin-1-standardized extract in advanced colorectal carcinoma. Onkologe 4 (Suppl 1): S35-9, 1998.</div></li><li><div class="bk_ref" id="CDR0000269596_rl_7_69">Wetzel D, Schäfer M: Results of a randomised placebo-controlled multicentre study with PS76A2 (standardised mistletoe preparation) in patients with breast cancer receiving adjuvant chemotherapy. [Abstract] Phytomedicine 7 (Suppl 2): A-SL-66, 2000.</div></li><li><div class="bk_ref" id="CDR0000269596_rl_7_70">Cho JS, Na KJ, Lee Y, et al.: Chemical Pleurodesis Using Mistletoe Extraction (ABNOVAviscum(®) Injection) for Malignant Pleural Effusion. Ann Thorac Cardiovasc Surg 22 (1): 20-6, 2016. [<a href="/pmc/articles/PMC4981776/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4981776</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26639937" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26639937</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_7_71">Viscum album. In: Homoeopathic Pharmacopoeia Convention of the United States: Homoeopathic Pharmacopoeia of the United States. 2002, Monograph 9444 Visc.</div></li></ol></div></div><div id="CDR0000269596__17"><h2 id="_CDR0000269596__17_">History</h2><p id="CDR0000269596__18"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285939/" class="def">Mistletoe</a> has been used for centuries for its medicinal properties.[<a class="bibr" href="#CDR0000269596_rl_17_1" rid="CDR0000269596_rl_17_1">1</a>-
|
|
<a class="bibr" href="#CDR0000269596_rl_17_6" rid="CDR0000269596_rl_17_6">6</a>] It was reportedly used by the Druids and the ancient Greeks, and it appears in legend and folklore as a <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044073/" class="def">panacea</a>. It has been used in various forms to treat <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045333/" class="def">cancer</a>, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044028/" class="def">epilepsy</a>, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046348/" class="def">infertility</a>, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046296/" class="def">menopausal</a> symptoms, nervous tension, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000440101/" class="def">asthma</a>, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044038/" class="def">hypertension</a>, headache, and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045667/" class="def">dermatitis</a>. The use of mistletoe in the treatment of cancer is about 100 years old, and its use in the treatment of other indications is much older. Modern interest in mistletoe as an anticancer treatment began in the 1920s. Most of the results of clinical studies have been published exclusively in German. For more information, see the <a href="#CDR0000269596__35">Human/Clinical Studies</a> section.</p><p id="CDR0000269596__19"> Another reported activity of mistletoe that may be relevant to optimum functioning of the immune system in individuals with cancer is stabilization of the <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000044393/" class="def">DNA</a> in <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045993/" class="def">white blood cells</a>, including white blood cells that have been exposed to DNA-damaging <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045214/" class="def">chemotherapy</a> drugs.[<a class="bibr" href="#CDR0000269596_rl_17_7" rid="CDR0000269596_rl_17_7">7</a>-<a class="bibr" href="#CDR0000269596_rl_17_11" rid="CDR0000269596_rl_17_11">11</a>]</p><p id="CDR0000269596__20">Mistletoe has been shown to stimulate increases in the number and the activity of various types of white blood cells.[<a class="bibr" href="#CDR0000269596_rl_17_2" rid="CDR0000269596_rl_17_2">2</a>,<a class="bibr" href="#CDR0000269596_rl_17_3" rid="CDR0000269596_rl_17_3">3</a>,<a class="bibr" href="#CDR0000269596_rl_17_9" rid="CDR0000269596_rl_17_9">9</a>,<a class="bibr" href="#CDR0000269596_rl_17_11" rid="CDR0000269596_rl_17_11">11</a>-<a class="bibr" href="#CDR0000269596_rl_17_53" rid="CDR0000269596_rl_17_53">53</a>] Immune system–enhancing <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046130/" class="def">cytokines</a>, such as <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000350231/" class="def">interleukin-1</a>, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044045/" class="def">interleukin-6</a>, and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045290/" class="def">tumor necrosis factor</a>-alpha, are released by white blood cells after exposure to mistletoe <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000407760/" class="def">extracts</a>.[<a class="bibr" href="#CDR0000269596_rl_17_1" rid="CDR0000269596_rl_17_1">1</a>,<a class="bibr" href="#CDR0000269596_rl_17_3" rid="CDR0000269596_rl_17_3">3</a>,<a class="bibr" href="#CDR0000269596_rl_17_7" rid="CDR0000269596_rl_17_7">7</a>,<a class="bibr" href="#CDR0000269596_rl_17_9" rid="CDR0000269596_rl_17_9">9</a>-<a class="bibr" href="#CDR0000269596_rl_17_11" rid="CDR0000269596_rl_17_11">11</a>,<a class="bibr" href="#CDR0000269596_rl_17_14" rid="CDR0000269596_rl_17_14">14</a>,<a class="bibr" href="#CDR0000269596_rl_17_19" rid="CDR0000269596_rl_17_19">19</a>,<a class="bibr" href="#CDR0000269596_rl_17_29" rid="CDR0000269596_rl_17_29">29</a>,<a class="bibr" href="#CDR0000269596_rl_17_33" rid="CDR0000269596_rl_17_33">33</a>,<a class="bibr" href="#CDR0000269596_rl_17_37" rid="CDR0000269596_rl_17_37">37</a>,<a class="bibr" href="#CDR0000269596_rl_17_42" rid="CDR0000269596_rl_17_42">42</a>-<a class="bibr" href="#CDR0000269596_rl_17_46" rid="CDR0000269596_rl_17_46">46</a>,<a class="bibr" href="#CDR0000269596_rl_17_48" rid="CDR0000269596_rl_17_48">48</a>-<a class="bibr" href="#CDR0000269596_rl_17_50" rid="CDR0000269596_rl_17_50">50</a>,<a class="bibr" href="#CDR0000269596_rl_17_52" rid="CDR0000269596_rl_17_52">52</a>-<a class="bibr" href="#CDR0000269596_rl_17_54" rid="CDR0000269596_rl_17_54">54</a>] Other evidence suggests that mistletoe exerts its <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044020/" class="def">cytotoxic</a> effects by interfering with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046092/" class="def">protein</a> synthesis in target cells [<a class="bibr" href="#CDR0000269596_rl_17_3" rid="CDR0000269596_rl_17_3">3</a>,<a class="bibr" href="#CDR0000269596_rl_17_4" rid="CDR0000269596_rl_17_4">4</a>,<a class="bibr" href="#CDR0000269596_rl_17_8" rid="CDR0000269596_rl_17_8">8</a>,<a class="bibr" href="#CDR0000269596_rl_17_11" rid="CDR0000269596_rl_17_11">11</a>,<a class="bibr" href="#CDR0000269596_rl_17_33" rid="CDR0000269596_rl_17_33">33</a>,<a class="bibr" href="#CDR0000269596_rl_17_42" rid="CDR0000269596_rl_17_42">42</a>-<a class="bibr" href="#CDR0000269596_rl_17_46" rid="CDR0000269596_rl_17_46">46</a>,<a class="bibr" href="#CDR0000269596_rl_17_52" rid="CDR0000269596_rl_17_52">52</a>,<a class="bibr" href="#CDR0000269596_rl_17_55" rid="CDR0000269596_rl_17_55">55</a>-<a class="bibr" href="#CDR0000269596_rl_17_63" rid="CDR0000269596_rl_17_63">63</a>] and by inducing <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046524/" class="def">apoptosis</a>.[<a class="bibr" href="#CDR0000269596_rl_17_3" rid="CDR0000269596_rl_17_3">3</a>,<a class="bibr" href="#CDR0000269596_rl_17_11" rid="CDR0000269596_rl_17_11">11</a>,<a class="bibr" href="#CDR0000269596_rl_17_36" rid="CDR0000269596_rl_17_36">36</a>,<a class="bibr" href="#CDR0000269596_rl_17_42" rid="CDR0000269596_rl_17_42">42</a>,<a class="bibr" href="#CDR0000269596_rl_17_46" rid="CDR0000269596_rl_17_46">46</a>,<a class="bibr" href="#CDR0000269596_rl_17_52" rid="CDR0000269596_rl_17_52">52</a>,<a class="bibr" href="#CDR0000269596_rl_17_64" rid="CDR0000269596_rl_17_64">64</a>-<a class="bibr" href="#CDR0000269596_rl_17_66" rid="CDR0000269596_rl_17_66">66</a>] Mistletoe may also serve a bridging function, bringing together immune system <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044024/" class="def">effector cells</a> and tumor cells.[<a class="bibr" href="#CDR0000269596_rl_17_18" rid="CDR0000269596_rl_17_18">18</a>,<a class="bibr" href="#CDR0000269596_rl_17_67" rid="CDR0000269596_rl_17_67">67</a>]</p><div id="CDR0000269596_rl_17"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000269596_rl_17_1">Capernaros Z: The golden bough: the case for mistletoe. Eur J Herbal Med 1 (1):19-24, 1994.</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_2">Mistletoe. In: Murray MT: The Healing Power of Herbs. Prima Publishing, 1995, pp 253-9.</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_3">Samtleben R, Hajto T, Hostanska K, et al.: Mistletoe lectins as immunostimulants (chemistry, pharmacology and clinic). In: Wagner H, ed.: Immunomodulatory Agents from Plants. Birkhauser Verlag, 1999, pp 223-41.</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_4">Olsnes S, Stirpe F, Sandvig K, et al.: Isolation and characterization of viscumin, a toxic lectin from Viscum album L. (mistletoe). J Biol Chem 257 (22): 13263-70, 1982. [<a href="https://pubmed.ncbi.nlm.nih.gov/7142144" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7142144</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_5">Becker H: Botany of European mistletoe (Viscum album L.). 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[<a href="https://pubmed.ncbi.nlm.nih.gov/11317168" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11317168</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_39">Heiny BM, Albrecht V, Beuth J: Correlation of immune cell activities and beta-endorphin release in breast carcinoma patients treated with galactose-specific lectin standardized mistletoe extract. Anticancer Res 18 (1B): 583-6, 1998 Jan-Feb. [<a href="https://pubmed.ncbi.nlm.nih.gov/9568181" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9568181</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_40">Stein GM, Schaller G, Pfüller U, et al.: Characterisation of granulocyte stimulation by thionins from European mistletoe and from wheat. Biochim Biophys Acta 1426 (1): 80-90, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/9878694" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9878694</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_41">Stein GM, Schaller G, Pfüller U, et al.: Thionins from Viscum album L: influence of the viscotoxins on the activation of granulocytes. Anticancer Res 19 (2A): 1037-42, 1999 Mar-Apr. [<a href="https://pubmed.ncbi.nlm.nih.gov/10368652" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10368652</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_42">Mengs U, Göthel D, Leng-Peschlow E: Mistletoe extracts standardized to mistletoe lectins in oncology: review on current status of preclinical research. Anticancer Res 22 (3): 1399-407, 2002 May-Jun. [<a href="https://pubmed.ncbi.nlm.nih.gov/12168816" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12168816</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_43">Bocci V: Mistletoe (viscum album) lectins as cytokine inducers and immunoadjuvant in tumor therapy. A review. J Biol Regul Homeost Agents 7 (1): 1-6, 1993 Jan-Mar. [<a href="https://pubmed.ncbi.nlm.nih.gov/8346712" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8346712</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_44">Gabius HJ, Gabius S, Joshi SS, et al.: From ill-defined extracts to the immunomodulatory lectin: will there be a reason for oncological application of mistletoe? Planta Med 60 (1): 2-7, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/8134410" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8134410</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_45">Zee-Cheng RK: Anticancer research on Loranthaceae plants. Drugs Future 22 (5): 519-30, 1997.</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_46">Kaegi E: Unconventional therapies for cancer: 3. Iscador. Task Force on Alternative Therapies of the Canadian Breast Cancer Research Initiative. CMAJ 158 (9): 1157-9, 1998. 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[<a href="https://pubmed.ncbi.nlm.nih.gov/10928154" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10928154</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_48">Goebell PJ, Otto T, Suhr J, et al.: Evaluation of an unconventional treatment modality with mistletoe lectin to prevent recurrence of superficial bladder cancer: a randomized phase II trial. J Urol 168 (1): 72-5, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/12050495" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12050495</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_49">Schaefermeyer G, Schaefermeyer H: Treatment of pancreatic cancer with Viscum album (Iscador): a retrospective study of 292 patients 1986-1996. Complement Ther Med 6 (4): 172-7, 1998.</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_50">Kunze E, Schulz H, Gabius HJ: Inability of galactoside-specific mistletoe lectin to inhibit N-methyl-N-nitrosourea-induced tumor development in the urinary bladder of rats and to mediate a local cellular immune response after long-term administration. J Cancer Res Clin Oncol 124 (2): 73-87, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9654190" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9654190</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_51">Kunze E, Schulz H, Adamek M, et al.: Long-term administration of galactoside-specific mistletoe lectin in an animal model: no protection against N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder carcinogenesis in rats and no induction of a relevant local cellular immune response. J Cancer Res Clin Oncol 126 (3): 125-38, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/10741906" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10741906</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_52">Mengs U, Schwarz T, Bulitta M, et al.: Antitumoral effects of an intravesically applied aqueous mistletoe extract on urinary bladder carcinoma MB49 in mice. Anticancer Res 20 (5B): 3565-8, 2000 Sep- Oct. [<a href="https://pubmed.ncbi.nlm.nih.gov/11131663" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11131663</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_53">Stauder H, Kreuser ED: Mistletoe extracts standardised in terms of mistletoe lectins (ML I) in oncology: current state of clinical research. Onkologie 25 (4): 374-80, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/12232491" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12232491</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_54">Kleijnen J, Knipschild P: Mistletoe treatment for cancer: review of controlled trials in humans. Phytomedicine 1: 255-60, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/23195947" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23195947</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_55">Stirpe F, Sandvig K, Olsnes S, et al.: Action of viscumin, a toxic lectin from mistletoe, on cells in culture. J Biol Chem 257 (22): 13271-7, 1982. [<a href="https://pubmed.ncbi.nlm.nih.gov/7142145" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7142145</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_56">Walzel H, Jonas L, Rosin T, et al.: Relationship between internalization kinetics and cytotoxicity of mistletoe lectin I to L1210 leukaemia cells. Folia Biol (Praha) 36 (3-4): 181-8, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2257937" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2257937</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_57">Franz H: Mistletoe lectins and their A and B chains. Oncology 43 (Suppl 1): 23-34, 1986. [<a href="https://pubmed.ncbi.nlm.nih.gov/3543782" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3543782</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_58">Sweeney EC, Palmer RA, Pfüller U: Crystallization of the ribosome inactivating protein ML1 from Viscum album (mistletoe) complexed with beta-D-galactose. J Mol Biol 234 (4): 1279-81, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8263931" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8263931</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_59">Jung ML, Baudino S, Ribéreau-Gayon G, et al.: Characterization of cytotoxic proteins from mistletoe (Viscum album L.). Cancer Lett 51 (2): 103-8, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2344587" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2344587</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_60">Gabius HJ, Darro F, Remmelink M, et al.: Evidence for stimulation of tumor proliferation in cell lines and histotypic cultures by clinically relevant low doses of the galactoside-binding mistletoe lectin, a component of proprietary extracts. Cancer Invest 19 (2): 114-26, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11296616" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11296616</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_61">Dietrich JB, Ribéreau-Gayon G, Jung ML, et al.: Identity of the N-terminal sequences of the three A chains of mistletoe (Viscum album L.) lectins: homology with ricin-like plant toxins and single-chain ribosome-inhibiting proteins. Anticancer Drugs 3 (5): 507-11, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1450445" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1450445</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_62">Jäggy C, Musielski H, Urech K, et al.: Quantitative determination of lectins in mistletoe preparations. Arzneimittelforschung 45 (8): 905-9, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7575759" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7575759</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_63">Burger AM, Mengs U, Schüler JB, et al.: Anticancer activity of an aqueous mistletoe extract (AME) in syngeneic murine tumor models. Anticancer Res 21 (3B): 1965-8, 2001 May-Jun. [<a href="https://pubmed.ncbi.nlm.nih.gov/11497284" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11497284</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_64">Janssen O, Scheffler A, Kabelitz D: In vitro effects of mistletoe extracts and mistletoe lectins. Cytotoxicity towards tumor cells due to the induction of programmed cell death (apoptosis). Arzneimittelforschung 43 (11): 1221-7, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8292069" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8292069</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_65">Zarkovic N, Vukovic T, Loncaric I, et al.: An overview on anticancer activities of the Viscum album extract Isorel. Cancer Biother Radiopharm 16 (1): 55-62, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11279798" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11279798</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_66">Maier G, Fiebig HH: Absence of tumor growth stimulation in a panel of 16 human tumor cell lines by mistletoe extracts in vitro. Anticancer Drugs 13 (4): 373-9, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/11984083" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11984083</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_17_67">Mueller EA, Anderer FA: Chemical specificity of effector cell/tumor cell bridging by a Viscum album rhamnogalacturonan enhancing cytotoxicity of human NK cells. Immunopharmacology 19 (1): 69-77, 1990 Jan-Feb. [<a href="https://pubmed.ncbi.nlm.nih.gov/2407685" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2407685</span></a>]</div></li></ol></div></div><div id="CDR0000269596__23"><h2 id="_CDR0000269596__23_">Laboratory/Animal/Preclinical Studies</h2><p id="CDR0000269596__24">The <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046356/" class="def">immune system</a>–stimulating and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044020/" class="def">cytotoxic</a> properties of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285939/" class="def">mistletoe</a> have been investigated in <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044512/" class="def">laboratory</a> and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000454774/" class="def">animal studies</a>.</p><p id="CDR0000269596__21">
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044094/" class="def">Viscotoxins</a> and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044051/" class="def">lectins</a> have been investigated as active components in mistletoe; most research has focused on the lectins.[<a class="bibr" href="#CDR0000269596_rl_23_1" rid="CDR0000269596_rl_23_1">1</a>-<a class="bibr" href="#CDR0000269596_rl_23_9" rid="CDR0000269596_rl_23_9">9</a>] Purified <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044994/" class="def">mistletoe lectins</a> have demonstrated cytotoxic and immune system–stimulating activities. Four different lectins have been identified in mistletoe <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000407760/" class="def">extracts</a> as follows:</p><ul id="CDR0000269596__281"><li class="half_rhythm"><div>ML-1.</div></li><li class="half_rhythm"><div>ML-2.</div></li><li class="half_rhythm"><div>ML-3.</div></li><li class="half_rhythm"><div><i>Viscum album</i>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285965/" class="def">chitin</a>-binding <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285953/" class="def">agglutinin</a>.</div></li></ul><p id="CDR0000269596__282">ML-1 (or viscumin) may be responsible for many of mistletoe’s <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044510/" class="def">biological</a> effects. When a laboratory method was used to selectively deplete ML-1 from <i>Viscum album</i> extracts, their cytotoxic and immune system–stimulating properties were markedly reduced.[<a class="bibr" href="#CDR0000269596_rl_23_10" rid="CDR0000269596_rl_23_10">10</a>,<a class="bibr" href="#CDR0000269596_rl_23_11" rid="CDR0000269596_rl_23_11">11</a>] It should be noted that fermentation eliminates most of the ML-1 in mistletoe extracts. Iscador, and other fermented mistletoe extracts, contain only the mistletoe lectins ML-2 and ML-3, whereas the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046092/" class="def">proteins</a> of the ML-1 complex are missing.[<a class="bibr" href="#CDR0000269596_rl_23_12" rid="CDR0000269596_rl_23_12">12</a>-<a class="bibr" href="#CDR0000269596_rl_23_14" rid="CDR0000269596_rl_23_14">14</a>] <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044162/" class="def">Polysaccharide</a> and oligosaccharide components of mistletoe extracts with substantial immune-stimulating properties have been reviewed.[<a class="bibr" href="#CDR0000269596_rl_23_15" rid="CDR0000269596_rl_23_15">15</a>,<a class="bibr" href="#CDR0000269596_rl_23_16" rid="CDR0000269596_rl_23_16">16</a>]</p><p id="CDR0000269596__61">The molecular structure of ML-1 consists of an alpha chain and a beta chain, which can be separated from one another.[<a class="bibr" href="#CDR0000269596_rl_23_1" rid="CDR0000269596_rl_23_1">1</a>,<a class="bibr" href="#CDR0000269596_rl_23_6" rid="CDR0000269596_rl_23_6">6</a>-<a class="bibr" href="#CDR0000269596_rl_23_9" rid="CDR0000269596_rl_23_9">9</a>,<a class="bibr" href="#CDR0000269596_rl_23_13" rid="CDR0000269596_rl_23_13">13</a>,<a class="bibr" href="#CDR0000269596_rl_23_17" rid="CDR0000269596_rl_23_17">17</a>,<a class="bibr" href="#CDR0000269596_rl_23_18" rid="CDR0000269596_rl_23_18">18</a>] Each chain type appears to mediate a subset of the activities described for the intact lectin. Cytotoxicity is associated mainly with the alpha chain. In <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044512/" class="def">laboratory
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studies</a>, the ML-1 alpha chain has been coupled to <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046066/" class="def">monoclonal antibodies</a> to produce <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045730/" class="def">immunotoxins</a> that target and kill specific cell types.[<a class="bibr" href="#CDR0000269596_rl_23_19" rid="CDR0000269596_rl_23_19">19</a>-<a class="bibr" href="#CDR0000269596_rl_23_21" rid="CDR0000269596_rl_23_21">21</a>]</p><p id="CDR0000269596__104"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044619/" class="def">Recombinant</a> ML-1, rML (also known as rViscumin or aviscumine) appears to have the same <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000346517/" class="def">efficacy</a> as plant-based ML-1 in laboratory studies.[<a class="bibr" href="#CDR0000269596_rl_23_22" rid="CDR0000269596_rl_23_22">22</a>] Because this is not an extract of mistletoe, it is out of the purview of this summary.</p><p id="CDR0000269596__105">The beta chain of ML-1 is responsible for binding to the surface of a target cell.[<a class="bibr" href="#CDR0000269596_rl_23_23" rid="CDR0000269596_rl_23_23">23</a>] Studies of mistletoe lectin binding to cancer cells have examined whether the extent of cell binding can predict disease <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000467853/" class="def">outcome</a> or survival. Studies show that the prognostic value of ML-1 binding depends on the type of cancer.[<a class="bibr" href="#CDR0000269596_rl_23_24" rid="CDR0000269596_rl_23_24">24</a>] For human <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000444971/" class="def">breast cancer</a> cells, the amount of lectin-bound cells correlates positively with disease outcome. However, for human <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046216/" class="def">adenocarcinoma</a> of the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000270740/" class="def">lung</a>, there is no correlation between the amount of lectin-bound cells and disease survival.[<a class="bibr" href="#CDR0000269596_rl_23_25" rid="CDR0000269596_rl_23_25">25</a>] Though much research has looked at this particular aspect, there have not been studies that directly link the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000683342/" class="def">concentration</a> of that component to any clinical activity of mistletoe.</p><p id="CDR0000269596__25">Laboratory studies have shown that mistletoe extracts can stimulate the activity of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045993/" class="def">white blood cells</a>
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<i><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045733/" class="def">in vitro</a></i> and cause them to release <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045065/" class="def">molecules</a> thought to be important for anticancer <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045722/" class="def">immune responses</a>.[<a class="bibr" href="#CDR0000269596_rl_23_4" rid="CDR0000269596_rl_23_4">4</a>,<a class="bibr" href="#CDR0000269596_rl_23_6" rid="CDR0000269596_rl_23_6">6</a>,<a class="bibr" href="#CDR0000269596_rl_23_8" rid="CDR0000269596_rl_23_8">8</a>,<a class="bibr" href="#CDR0000269596_rl_23_9" rid="CDR0000269596_rl_23_9">9</a>,<a class="bibr" href="#CDR0000269596_rl_23_17" rid="CDR0000269596_rl_23_17">17</a>,<a class="bibr" href="#CDR0000269596_rl_23_26" rid="CDR0000269596_rl_23_26">26</a>-<a class="bibr" href="#CDR0000269596_rl_23_33" rid="CDR0000269596_rl_23_33">33</a>] In addition, mistletoe extracts have demonstrated cytotoxic activity against a variety of mouse, rat, and human <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045333/" class="def">cancer</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046476/" class="def">cells</a>
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<i>in vitro</i>.[<a class="bibr" href="#CDR0000269596_rl_23_1" rid="CDR0000269596_rl_23_1">1</a>,<a class="bibr" href="#CDR0000269596_rl_23_8" rid="CDR0000269596_rl_23_8">8</a>,<a class="bibr" href="#CDR0000269596_rl_23_23" rid="CDR0000269596_rl_23_23">23</a>,<a class="bibr" href="#CDR0000269596_rl_23_34" rid="CDR0000269596_rl_23_34">34</a>-<a class="bibr" href="#CDR0000269596_rl_23_37" rid="CDR0000269596_rl_23_37">37</a>] </p><p id="CDR0000269596__118">There are conflicting reports concerning the stimulation of cancer cell growth <i>in vitro</i>. In one study, the <i>in vitro</i> growth of several types of human cancer cells was stimulated by treatment with low <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044664/" class="def">doses</a> of the purified <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044051/" class="def">lectin</a> ML-1.[<a class="bibr" href="#CDR0000269596_rl_23_1" rid="CDR0000269596_rl_23_1">1</a>] However, various other studies found that ML-1 and mistletoe extracts did not induce <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046479/" class="def">cell proliferation</a>.[<a class="bibr" href="#CDR0000269596_rl_23_38" rid="CDR0000269596_rl_23_38">38</a>,<a class="bibr" href="#CDR0000269596_rl_23_39" rid="CDR0000269596_rl_23_39">39</a>]</p><p id="CDR0000269596__255"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044517/" class="def">Preclinical studies</a> demonstrating biological effects on <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000695994/" class="def">cancer cell lines</a> and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000043996/" class="def">animal models</a> are summarized in <a href="/books/NBK66054/table/CDR0000269596__257/?report=objectonly" target="object" rid-ob="figobCDR0000269596257">Table 1</a> and <a href="/books/NBK66054/table/CDR0000269596__258/?report=objectonly" target="object" rid-ob="figobCDR0000269596258">Table 2</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figCDR0000269596257"><a href="/books/NBK66054/table/CDR0000269596__257/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobCDR0000269596257"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="CDR0000269596__257"><a href="/books/NBK66054/table/CDR0000269596__257/?report=objectonly" target="object" rid-ob="figobCDR0000269596257">Table</a></h4><p class="float-caption no_bottom_margin">Table 1. <i>In Vitro</i> Studies<sup>a</sup>. </p></div></div><p id="CDR0000269596__256">Studies of the ability of mistletoe to inhibit cancer cell growth in animals have yielded mixed and inconsistent results.[<a class="bibr" href="#CDR0000269596_rl_23_5" rid="CDR0000269596_rl_23_5">5</a>-<a class="bibr" href="#CDR0000269596_rl_23_9" rid="CDR0000269596_rl_23_9">9</a>,<a class="bibr" href="#CDR0000269596_rl_23_36" rid="CDR0000269596_rl_23_36">36</a>,<a class="bibr" href="#CDR0000269596_rl_23_42" rid="CDR0000269596_rl_23_42">42</a>-<a class="bibr" href="#CDR0000269596_rl_23_50" rid="CDR0000269596_rl_23_50">50</a>] In most of these studies, mistletoe extracts were administered either by <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045914/" class="def">subcutaneous</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044678/" class="def">injection</a> or by <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046339/" class="def">intraperitoneal</a> injection; some of the differences in results may have resulted from the difference in route of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000478733/" class="def">administration</a>. For example, IscadorM administration was associated with a prolonged survival of female Swiss mice when the route of administration was intraperitoneal [<a class="bibr" href="#CDR0000269596_rl_23_51" rid="CDR0000269596_rl_23_51">51</a>] but not when the route was subcutaneous.[<a class="bibr" href="#CDR0000269596_rl_23_52" rid="CDR0000269596_rl_23_52">52</a>] Other differences between these two studies were the number of cells used in the Ehrlich <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045601/" class="def">ascites</a> inoculum and the doses of IscadorM administered.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figCDR0000269596258"><a href="/books/NBK66054/table/CDR0000269596__258/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobCDR0000269596258"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="CDR0000269596__258"><a href="/books/NBK66054/table/CDR0000269596__258/?report=objectonly" target="object" rid-ob="figobCDR0000269596258">Table</a></h4><p class="float-caption no_bottom_margin">Table 2. <i>In Vivo</i> Studies<sup>a</sup>. </p></div></div><div id="CDR0000269596_rl_23"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000269596_rl_23_1">Gabius HJ, Darro F, Remmelink M, et al.: Evidence for stimulation of tumor proliferation in cell lines and histotypic cultures by clinically relevant low doses of the galactoside-binding mistletoe lectin, a component of proprietary extracts. Cancer Invest 19 (2): 114-26, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11296616" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11296616</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_2">Lenartz D, Dott U, Menzel J, et al.: Survival of glioma patients after complementary treatment with galactoside-specific lectin from mistletoe. Anticancer Res 20 (3B): 2073-6, 2000 May-Jun. [<a href="https://pubmed.ncbi.nlm.nih.gov/10928154" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10928154</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_3">Steuer-Vogt MK, Bonkowsky V, Ambrosch P, et al.: The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial. Eur J Cancer 37 (1): 23-31, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11165126" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11165126</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_4">Goebell PJ, Otto T, Suhr J, et al.: Evaluation of an unconventional treatment modality with mistletoe lectin to prevent recurrence of superficial bladder cancer: a randomized phase II trial. J Urol 168 (1): 72-5, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/12050495" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12050495</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_5">Kunze E, Schulz H, Adamek M, et al.: Long-term administration of galactoside-specific mistletoe lectin in an animal model: no protection against N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder carcinogenesis in rats and no induction of a relevant local cellular immune response. J Cancer Res Clin Oncol 126 (3): 125-38, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/10741906" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10741906</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_6">Mengs U, Schwarz T, Bulitta M, et al.: Antitumoral effects of an intravesically applied aqueous mistletoe extract on urinary bladder carcinoma MB49 in mice. Anticancer Res 20 (5B): 3565-8, 2000 Sep- Oct. [<a href="https://pubmed.ncbi.nlm.nih.gov/11131663" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11131663</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_7">Burger AM, Mengs U, Schüler JB, et al.: Anticancer activity of an aqueous mistletoe extract (AME) in syngeneic murine tumor models. Anticancer Res 21 (3B): 1965-8, 2001 May-Jun. [<a href="https://pubmed.ncbi.nlm.nih.gov/11497284" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11497284</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_8">Mengs U, Göthel D, Leng-Peschlow E: Mistletoe extracts standardized to mistletoe lectins in oncology: review on current status of preclinical research. Anticancer Res 22 (3): 1399-407, 2002 May-Jun. [<a href="https://pubmed.ncbi.nlm.nih.gov/12168816" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12168816</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_9">Samtleben R, Hajto T, Hostanska K, et al.: Mistletoe lectins as immunostimulants (chemistry, pharmacology and clinic). In: Wagner H, ed.: Immunomodulatory Agents from Plants. Birkhauser Verlag, 1999, pp 223-41.</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_10">Janssen O, Scheffler A, Kabelitz D: In vitro effects of mistletoe extracts and mistletoe lectins. Cytotoxicity towards tumor cells due to the induction of programmed cell death (apoptosis). Arzneimittelforschung 43 (11): 1221-7, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8292069" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8292069</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_11">Beuth J, Stoffel B, Ko HL, et al.: Immunomodulating ability of galactoside-specific lectin standardized and depleted mistletoe extract. Arzneimittelforschung 45 (11): 1240-2, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/8929248" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8929248</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_12">Wagner H, Jordan E, Feil B: Studies on the standardization of mistletoe preparations. Oncology 43 (Suppl 1): 16-22, 1986. [<a href="https://pubmed.ncbi.nlm.nih.gov/3027640" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3027640</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_13">Mistletoe. In: Murray MT: The Healing Power of Herbs. Prima Publishing, 1995, pp 253-9.</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_14">Jäggy C, Musielski H, Urech K, et al.: Quantitative determination of lectins in mistletoe preparations. Arzneimittelforschung 45 (8): 905-9, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7575759" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7575759</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_15">Stein GM, Büssing A, Schietzel M: Stimulation of the maturation of dendritic cells in vitro by a fermented mistletoe extract. Anticancer Res 22 (6C): 4215-9, 2002 Nov-Dec. [<a href="https://pubmed.ncbi.nlm.nih.gov/12553059" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12553059</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_16">Lyu SY, Kwon YJ, Joo HJ, et al.: Preparation of alginate/chitosan microcapsules and enteric coated granules of mistletoe lectin. Arch Pharm Res 27 (1): 118-26, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/14969350" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14969350</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_17">Timoshenko AV, Gabius HJ: Efficient induction of superoxide release from human neutrophils by the galactoside-specific lectin from Viscum album. Biol Chem Hoppe Seyler 374 (4): 237-43, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8392351" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8392351</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_18">Dietrich JB, Ribéreau-Gayon G, Jung ML, et al.: Identity of the N-terminal sequences of the three A chains of mistletoe (Viscum album L.) lectins: homology with ricin-like plant toxins and single-chain ribosome-inhibiting proteins. Anticancer Drugs 3 (5): 507-11, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1450445" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1450445</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_19">Wiedłocha A, Sandvig K, Walzel H, et al.: Internalization and action of an immunotoxin containing mistletoe lectin A-chain. Cancer Res 51 (3): 916-20, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/1988131" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1988131</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_20">Tonevitsky AG, Toptygin AYu, Pfuller U, et al.: Immunotoxin with mistletoe lectin I A-chain and ricin A-chain directed against CD5 antigen of human T-lymphocytes; comparison of efficiency and specificity. Int J Immunopharmacol 13 (7): 1037-41, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/1722193" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1722193</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_21">Bocci V: Mistletoe (viscum album) lectins as cytokine inducers and immunoadjuvant in tumor therapy. A review. J Biol Regul Homeost Agents 7 (1): 1-6, 1993 Jan-Mar. [<a href="https://pubmed.ncbi.nlm.nih.gov/8346712" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8346712</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_22">Habeck M: Mistletoe compound enters clinical trials. Drug Discov Today 8 (2): 52-3, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/12565000" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12565000</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_23">Müthing J, Meisen I, Kniep B, et al.: Tumor-associated CD75s gangliosides and CD75s-bearing glycoproteins with Neu5Acalpha2-6Galbeta1-4GlcNAc-residues are receptors for the anticancer drug rViscumin. FASEB J 19 (1): 103-5, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/15520251" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15520251</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_24">Fritz P, Dippon J, Kierschke T, et al.: Impact of mistletoe lectin binding in breast cancer. Anticancer Res 24 (2C): 1187-92, 2004 Mar-Apr. [<a href="https://pubmed.ncbi.nlm.nih.gov/15154645" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15154645</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_25">Blonski K, Schumacher U, Burkholder I, et al.: Binding of recombinant mistletoe lectin (aviscumine) to resected human adenocarcinoma of the lung. Anticancer Res 25 (5): 3303-7, 2005 Sep-Oct. [<a href="https://pubmed.ncbi.nlm.nih.gov/16101142" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16101142</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_26">Timoshenko AV, Kayser K, Drings P, et al.: Modulation of lectin-triggered superoxide release from neutrophils of tumor patients with and without chemotherapy. Anticancer Res 13 (5C): 1789-92, 1993 Sep-Oct. [<a href="https://pubmed.ncbi.nlm.nih.gov/8267383" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8267383</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_27">Timoshenko AV, Gabius HJ: Influence of the galactoside-specific lectin from Viscum album and its subunits on cell aggregation and selected intracellular parameters of rat thymocytes. Planta Med 61 (2): 130-3, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7753919" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7753919</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_28">Timoshenko AV, Cherenkevich SN, Gabius HJ: Viscum album agglutinin-induced aggregation of blood cells and the lectin effects on neutrophil function. Biomed Pharmacother 49 (3): 153-8, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7647287" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7647287</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_29">Hostanska K, Hajto T, Spagnoli GC, et al.: A plant lectin derived from Viscum album induces cytokine gene expression and protein production in cultures of human peripheral blood mononuclear cells. Nat Immun 14 (5-6): 295-304, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/8933823" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8933823</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_30">Fischer S, Scheffler A, Kabelitz D: Oligoclonal in vitro response of CD4 T cells to vesicles of mistletoe extracts in mistletoe-treated cancer patients. Cancer Immunol Immunother 44 (3): 150-6, 1997. [<a href="/pmc/articles/PMC11037688/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC11037688</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/9191874" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9191874</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_31">Stein GM, Schaller G, Pfüller U, et al.: Characterisation of granulocyte stimulation by thionins from European mistletoe and from wheat. Biochim Biophys Acta 1426 (1): 80-90, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/9878694" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9878694</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_32">Stein GM, Schaller G, Pfüller U, et al.: Thionins from Viscum album L: influence of the viscotoxins on the activation of granulocytes. Anticancer Res 19 (2A): 1037-42, 1999 Mar-Apr. [<a href="https://pubmed.ncbi.nlm.nih.gov/10368652" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10368652</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_33">Hallek M: Interleukin-6-mediated cell growth in multiple myeloma--a role for Viscum album extracts? Onkologie 28 (8-9): 387, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/16160399" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16160399</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_34">Schaller G, Urech K, Giannattasio M: Cytotoxicity of different viscotoxins and extracts from the European subspecies Viscum album L. Phytother Res 10 (6): 473-7, 1996.</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_35">Maier G, Fiebig HH: Absence of tumor growth stimulation in a panel of 16 human tumor cell lines by mistletoe extracts in vitro. Anticancer Drugs 13 (4): 373-9, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/11984083" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11984083</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_36">Zarkovic N, Vukovic T, Loncaric I, et al.: An overview on anticancer activities of the Viscum album extract Isorel. Cancer Biother Radiopharm 16 (1): 55-62, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11279798" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11279798</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_37">Zuzak TJ, Rist L, Eggenschwiler J, et al.: Paediatric medulloblastoma cells are susceptible to Viscum album (Mistletoe) preparations. Anticancer Res 26 (5A): 3485-92, 2006 Sep-Oct. [<a href="https://pubmed.ncbi.nlm.nih.gov/17094471" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17094471</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_38">Kelter G, Fiebig HH: Absence of tumor growth stimulation in a panel of 26 human tumor cell lines by mistletoe (Viscum album L.) extracts Iscador in vitro. Arzneimittelforschung 56 (6A): 435-40, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16927523" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16927523</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_39">Kelter G, Schierholz JM, Fischer IU, et al.: Cytotoxic activity and absence of tumor growth stimulation of standardized mistletoe extracts in human tumor models in vitro. Anticancer Res 27 (1A): 223-33, 2007 Jan-Feb. [<a href="https://pubmed.ncbi.nlm.nih.gov/17352237" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17352237</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_40">Weissenstein U, Kunz M, Urech K, et al.: Interaction of standardized mistletoe (Viscum album) extracts with chemotherapeutic drugs regarding cytostatic and cytotoxic effects in vitro. BMC Complement Altern Med 14: 6, 2014. [<a href="/pmc/articles/PMC3893555/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3893555</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24397864" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24397864</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_41">Podlech O, Harter PN, Mittelbronn M, et al.: Fermented mistletoe extract as a multimodal antitumoral agent in gliomas. Evid Based Complement Alternat Med 2012: 501796, 2012. [<a href="/pmc/articles/PMC3485514/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3485514</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23133496" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23133496</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_42">Cebović T, Spasić S, Popović M: Cytotoxic effects of the Viscum album L. extract on Ehrlich tumour cells in vivo. Phytother Res 22 (8): 1097-103, 2008. [<a href="https://pubmed.ncbi.nlm.nih.gov/18570233" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18570233</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_43">Seifert G, Jesse P, Laengler A, et al.: Molecular mechanisms of mistletoe plant extract-induced apoptosis in acute lymphoblastic leukemia in vivo and in vitro. Cancer Lett 264 (2): 218-28, 2008. [<a href="https://pubmed.ncbi.nlm.nih.gov/18314258" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18314258</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_44">Thies A, Dautel P, Meyer A, et al.: Low-dose mistletoe lectin-I reduces melanoma growth and spread in a scid mouse xenograft model. Br J Cancer 98 (1): 106-12, 2008. [<a href="/pmc/articles/PMC2359693/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2359693</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18026191" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18026191</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_45">Van Huyen JP, Delignat S, Bayry J, et al.: Interleukin-12 is associated with the in vivo anti-tumor effect of mistletoe extracts in B16 mouse melanoma. Cancer Lett 243 (1): 32-7, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16412563" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16412563</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_46">Beuth J, Ko HL, Schneider H, et al.: Intratumoral application of standardized mistletoe extracts down regulates tumor weight via decreased cell proliferation, increased apoptosis and necrosis in a murine model. Anticancer Res 26 (6B): 4451-6, 2006 Nov-Dec. [<a href="https://pubmed.ncbi.nlm.nih.gov/17201168" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17201168</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_47">Braun JM, Ko HL, Schierholz JM, et al.: Standardized mistletoe extract augments immune response and down-regulates local and metastatic tumor growth in murine models. Anticancer Res 22 (6C): 4187-90, 2002 Nov-Dec. [<a href="https://pubmed.ncbi.nlm.nih.gov/12553054" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12553054</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_48">Pryme IF, Bardocz S, Pusztai A, et al.: Dietary mistletoe lectin supplementation and reduced growth of a murine non-Hodgkin lymphoma. Histol Histopathol 17 (1): 261-71, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/11820217" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11820217</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_49">Elsässer-Beile U, Ruhnau T, Freudenberg N, et al.: Antitumoral effect of recombinant mistletoe lectin on chemically induced urinary bladder carcinogenesis in a rat model. Cancer 91 (5): 998-1004, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11251952" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11251952</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_50">Stauder H, Kreuser ED: Mistletoe extracts standardised in terms of mistletoe lectins (ML I) in oncology: current state of clinical research. Onkologie 25 (4): 374-80, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/12232491" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12232491</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_51">Khwaja TA, Dias CB, Pentecost S: Recent studies on the anticancer activities of mistletoe (Viscum album) and its alkaloids. Oncology 43 (Suppl 1): 42-50, 1986. [<a href="https://pubmed.ncbi.nlm.nih.gov/3543783" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3543783</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_52">Berger M, Schmähl D: Studies on the tumor-inhibiting efficacy of Iscador in experimental animal tumors. J Cancer Res Clin Oncol 105 (3): 262-5, 1983. [<a href="https://pubmed.ncbi.nlm.nih.gov/6853588" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6853588</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_53">Rostock M, Huber R, Greiner T, et al.: Anticancer activity of a lectin-rich mistletoe extract injected intratumorally into human pancreatic cancer xenografts. Anticancer Res 25 (3B): 1969-75, 2005 May-Jun. [<a href="https://pubmed.ncbi.nlm.nih.gov/16158932" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16158932</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_23_54">Jurin M, Zarković N, Hrzenjak M, et al.: Antitumorous and immunomodulatory effects of the Viscum album L. preparation Isorel. Oncology 50 (6): 393-8, 1993 Nov-Dec. [<a href="https://pubmed.ncbi.nlm.nih.gov/8233280" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8233280</span></a>]</div></li></ol></div></div><div id="CDR0000269596__35"><h2 id="_CDR0000269596__35_">Human/Clinical Studies</h2><p id="CDR0000269596__36"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285939/" class="def">Mistletoe</a> has been evaluated as a treatment for people with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045333/" class="def">cancer</a> in numerous <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044195/" class="def">clinical studies</a>.[<a class="bibr" href="#CDR0000269596_rl_35_1" rid="CDR0000269596_rl_35_1">1</a>-<a class="bibr" href="#CDR0000269596_rl_35_20" rid="CDR0000269596_rl_35_20">20</a>] </p><p id="CDR0000269596__108">The mistletoe <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000407760/" class="def">extracts</a> and products studied in clinical trials were Iscador, Eurixor, Helixor, Lektinol, Isorel, abnobaVISCUM,[<a class="bibr" href="#CDR0000269596_rl_35_21" rid="CDR0000269596_rl_35_21">21</a>] and recombinant <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044051/" class="def">lectin</a> ML-1. For more information, see the appropriate subsections and tables in this section.</p><p id="CDR0000269596__197">The findings from more than 50 clinical trials of mistletoe extracts in patients with cancer have been published, and several systematic reviews and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000691484/" class="def">meta-analyses</a> of the results of these studies have been performed. Three of the most recent systematic reviews addressed <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045417/" class="def">quality of life</a> (QOL), survival, and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045022/" class="def">symptom</a> relief in patients with various cancer types.[<a class="bibr" href="#CDR0000269596_rl_35_18" rid="CDR0000269596_rl_35_18">18</a>,<a class="bibr" href="#CDR0000269596_rl_35_20" rid="CDR0000269596_rl_35_20">20</a>,<a class="bibr" href="#CDR0000269596_rl_35_22" rid="CDR0000269596_rl_35_22">22</a>] Most studies reported an improvement in QOL, as did a noncontrolled, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044160/" class="def">nonrandomized</a>, real-world
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study that analyzed patient registry data.[<a class="bibr" href="#CDR0000269596_rl_35_23" rid="CDR0000269596_rl_35_23">23</a>] </p><p id="CDR0000269596__198">In one systematic review that examined 26 <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045858/" class="def">randomized</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044014/" class="def">controlled trials</a> (RCTs), 22 trials reported an improvement in QOL. All 10 of the nonRCTs also reported the same benefit. Improvement in <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000321374/" class="def">fatigue</a>, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000390302/" class="def">nausea</a> and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000390324/" class="def">vomiting</a>, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000430479/" class="def">depression</a>, emotional well-being, and concentration were reported. Some of the studies were well designed, while others reported weaknesses.[<a class="bibr" href="#CDR0000269596_rl_35_22" rid="CDR0000269596_rl_35_22">22</a>]</p><p id="CDR0000269596__203"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046634/" class="def">Tumor</a> response, QOL, and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000454766/" class="def">psychological</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000454701/" class="def">distress</a> were measured in a review of 21 RCTs of various cancers in which different mistletoe preparations were used either alone, with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045214/" class="def">chemotherapy</a>, or with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044971/" class="def">radiation therapy</a>.[<a class="bibr" href="#CDR0000269596_rl_35_18" rid="CDR0000269596_rl_35_18">18</a>] Survival times were included in 13 of the studies. Most of the studies reported benefits for patients, although this review was limited by small sample size and methodological weaknesses. Thus, the authors were unable to suggest practice guidelines for the use of mistletoe.</p><p id="CDR0000269596__204">The oldest of these three reviews investigated the results of 10 RCTs that used a variety of mistletoe extracts in patients with various malignancies. There was no difference in survival or other benefits for cancer patients who received mistletoe. Therefore, mistletoe was not recommended as a <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000318813/" class="def">curative</a> or <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046609/" class="def">supportive care</a> therapy.[<a class="bibr" href="#CDR0000269596_rl_35_20" rid="CDR0000269596_rl_35_20">20</a>]</p><p id="CDR0000269596__37">A systematic review of all controlled clinical studies of mistletoe found consistent improvement in chemotherapy-associated fatigue as well as other QOL measures.[<a class="bibr" href="#CDR0000269596_rl_35_22" rid="CDR0000269596_rl_35_22">22</a>]</p><p id="CDR0000269596__38">Although mistletoe was found to be <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000043985/" class="def">therapeutically</a> effective in most of the reported studies, many of the studies had one or more major design weaknesses as mentioned above that raised doubts about the reliability of the findings. These weaknesses include the following: </p><ul id="CDR0000269596__283"><li class="half_rhythm"><div>Registration of small numbers of patients.</div></li><li class="half_rhythm"><div>Presence of large numbers of patients who either were not <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044029/" class="def">evaluable</a> or were otherwise excluded from the analyses.</div></li><li class="half_rhythm"><div>Failure to adequately document mistletoe use, mistletoe <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044664/" class="def">dose</a>, and/or interruptions of mistletoe use.</div></li><li class="half_rhythm"><div>Absence of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044149/" class="def">control subjects</a> or use of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044596/" class="def">historical control subjects</a>. </div></li><li class="half_rhythm"><div>Use of inadequate <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000322881/" class="def">randomization</a> procedures.</div></li><li class="half_rhythm"><div>Absence of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285982/" class="def">treatment blinding</a>.</div></li><li class="half_rhythm"><div>Extensive use of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285981/" class="def">subset analysis</a>.</div></li><li class="half_rhythm"><div>The measurement of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285973/" class="def">mean</a> as opposed to <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044941/" class="def">median</a> survival.</div></li></ul><p id="CDR0000269596__284">In addition, evaluation of the studies is often hindered by incomplete descriptions of the study design and by incomplete reporting of clinical data, including data about previous and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044011/" class="def">concurrent therapies</a> received by the patients. Note: In studies with small numbers of patients, the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285974/" class="def">mean survival time</a> can be greatly exaggerated if one or more patients exhibit unusually long survival; <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000655249/" class="def">median survival</a>, therefore, is a less biased measure. </p><p id="CDR0000269596__292">A selection of studies is discussed below, organized by the type of mistletoe extract used. Studies on Iscador are summarized in <a href="/books/NBK66054/table/CDR0000269596__194/?report=objectonly" target="object" rid-ob="figobCDR0000269596194">Table 3</a>. Studies on Helixor, abnobaVISCUM, Eurixor, Isorel, and Lektinol are summarized in <a href="/books/NBK66054/table/CDR0000269596__71/?report=objectonly" target="object" rid-ob="figobCDR000026959671">Table 4</a>. Eurixor, Isorel, and Vysorel are no longer available on the market for sale.</p><div id="CDR0000269596__125"><h3>Iscador</h3><div id="CDR0000269596__301"><h4>Quality of life</h4><div id="CDR0000269596__302"><h5>Miscellaneous cancers </h5><p id="CDR0000269596__303">Although the quality of literature is limited by methodological flaws, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044079/" class="def">prospective</a> and controlled studies that explored the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000346517/" class="def">efficacy</a> of Iscador use on QOL in patients with cancer generally report positive effects in favor of complementary treatment. A <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000691484/" class="def">meta-analysis</a> of several studies (RCTs: n = 9; non-RCTs: n = 4; patients n = 734) reported a <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044167/" class="def">statistically significant</a> overall treatment effect in favor of Iscador application (standard <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285973/" class="def">mean</a> deviation [SMD], 0.56; 95% confidence interval [CI], 0.41–0.71; <i>P</i> < .0001).[<a class="bibr" href="#CDR0000269596_rl_35_24" rid="CDR0000269596_rl_35_24">24</a>] Tumor localization and study design were not significantly associated with a better or worse study <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000467853/" class="def">outcome</a> following multivariable regression.</p></div><div id="CDR0000269596__304"><h5>Breast cancer</h5><p id="CDR0000269596__305">A randomized study of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000043980/" class="def">postoperative</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000446564/" class="def">early-stage breast cancer</a> patients (T1, 3N0, 2M0) who received <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045587/" class="def">adjuvant chemotherapy</a> with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045253/" class="def">cyclophosphamide,</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000346515/" class="def">Adriamycin</a>, and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046090/" class="def">fluorouracil</a> found that patients who also received IscadorM treatment, a <i>Viscum album</i> extract harvested from apple (Mali) trees (n = 30), had significantly superior QOL ratings compared with patients who received chemotherapy alone (n = 31) (95% CI, <i>P</i> ≤ .017).[<a class="bibr" href="#CDR0000269596_rl_35_7" rid="CDR0000269596_rl_35_7">7</a>] Significant improvements were noted in physical functioning, role functioning, emotional functioning, and social functioning. Improvements were also noted in <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000454699/" class="def">appetite</a>, nausea and vomiting, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000306496/" class="def">diarrhea</a>, fatigue, pain, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046183/" class="def">dyspnea</a>, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044043/" class="def">insomnia,</a> and financial difficulties.[<a class="bibr" href="#CDR0000269596_rl_35_7" rid="CDR0000269596_rl_35_7">7</a>] </p></div><div id="CDR0000269596__306"><h5>Non-small cell lung cancer (NSCLC) </h5><p id="CDR0000269596__307">At least two RCTs have assessed the QOL of patients with advanced NSCLC. Patients who received <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045182/" class="def">carboplatin</a>/<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000508951/" class="def">gemcitabine</a> or carboplatin/<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045456/" class="def">pemetrexed</a> and were randomly assigned to receive open-label IscadorQu treatment, a <i>Viscum album</i> extract harvested from oak (<i>Quercus</i>) trees, did not report statistically significant improvements in QOL when compared with NSCLC patients who received carboplatin-based combinations alone.[<a class="bibr" href="#CDR0000269596_rl_35_25" rid="CDR0000269596_rl_35_25">25</a>] An <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000430407/" class="def">assessment</a> of QOL was performed in a study of patients with NSCLC who received adjuvant chemotherapy with IscadorQu and IscadorU (harvested from elm [<i>Ulmi</i>] trees) or a <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044744/" class="def">vitamin</a> B mixture (control) over 2 years.[<a class="bibr" href="#CDR0000269596_rl_35_26" rid="CDR0000269596_rl_35_26">26</a>] A <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000330183/" class="def">subjective improvement</a> in general well-being was more often seen in patients treated with Iscador.</p></div><div id="CDR0000269596__308"><h5>Osteosarcoma</h5><p id="CDR0000269596__309">QOL was assessed as a secondary <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000346519/" class="def">endpoint</a> in a small (n = 20) study of patients with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045395/" class="def">osteosarcoma</a>. Patients were free from disease after their second <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044058/" class="def">metastatic</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045866/" class="def">relapse</a> and were randomly assigned to receive either open-label IscadorP <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044737/" class="def">therapy</a>, a <i>Viscum album</i> extract harvested from pine (Pini) trees, or <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044068/" class="def">oral</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045189/" class="def">etoposide</a>. Patients who received Iscador therapy experienced significant improvements in overall (global) and individual QOL domains when compared with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000467830/" class="def">baseline</a> functioning (global health/QOL; 95% CI, 2.62–19.72; <i>P</i> = .013).[<a class="bibr" href="#CDR0000269596_rl_35_27" rid="CDR0000269596_rl_35_27">27</a>] Improvements over baseline values were also reported in the following areas:</p><ul id="CDR0000269596__310"><li class="half_rhythm"><div>Physical functioning (95% CI, 0.15–14.44; <i>P</i> = .046).</div></li><li class="half_rhythm"><div>Social functioning (95% CI, 4.64–18.88; <i>P</i> = .003).</div></li><li class="half_rhythm"><div>Fatigue (95% CI, −16.31 to −3.38; <i>P</i> = .005).</div></li><li class="half_rhythm"><div>Pain (95% CI, −18.83 to −2.60; <i>P</i> = .012).</div></li><li class="half_rhythm"><div>Dyspnea (95% CI, −16.94 to −8.32; <i>P</i> < .0001). </div></li><li class="half_rhythm"><div>Financial difficulties (95% CI, −16.21 to −6.70; <i>P</i> < .0001).</div></li></ul></div><div id="CDR0000269596__311"><h5>Ovarian cancer </h5><p id="CDR0000269596__312"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000445074/" class="def">Ovarian cancer</a> patients without metastases (n = 21 pairs) were randomly assigned to receive adjuvant Iscador (host tree unspecified) or no further treatment. Significant improvements in QOL were noted, as assessed by the degree of <i>psychosomatic self-regulation</i>, described as the capacity for autonomous regulation of emotional, social, and psychological factors, within 12 months of treatment (estimated median difference: 0.58; 95% CI, 0.30–0.90; <i>P</i> = .0002).[<a class="bibr" href="#CDR0000269596_rl_35_11" rid="CDR0000269596_rl_35_11">11</a>] </p></div><div id="CDR0000269596__313"><h5>Uterine cancer </h5><p id="CDR0000269596__314">Secondary endpoint <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000390238/" class="def">analysis</a> of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000445094/" class="def">uterine cancer</a> patients without metastases (randomized: n = 30 pairs; nonrandomized: n = 103 pairs) who received adjuvant Iscador displayed significant improvements in psychosomatic self-regulation within 12 months of treatment when compared with women who received conventional oncological therapy alone (estimated median difference and 95% CI, 0.40 [0.15–0.70]; <i>P</i> = .0012; and 0.70 [0.25–1.15], <i>P</i> = .0037, respectively).[<a class="bibr" href="#CDR0000269596_rl_35_10" rid="CDR0000269596_rl_35_10">10</a>]</p></div></div><div id="CDR0000269596__315"><h4>Symptom management</h4><div id="CDR0000269596__316"><h5>Breast cancer</h5><p id="CDR0000269596__317">In a study of postoperative early-stage breast cancer patients (T1, 3N0, 2M0) who were randomly assigned to receive open-label IscadorM therapy after chemotherapy (n = 30), a secondary endpoint analysis did not demonstrate statistically significant improvements in <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045361/" class="def">neutropenia</a> (<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046270/" class="def">neutrophil</a> count <1,000/µL) when compared with patients who received chemotherapy alone (n = 31).[<a class="bibr" href="#CDR0000269596_rl_35_7" rid="CDR0000269596_rl_35_7">7</a>] </p><p id="CDR0000269596__318">Another study (retrolective design) of postoperative early-stage breast cancer patients (T2, 4N0, 2M0) who received adjuvant <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044950/" class="def">conventional treatment</a> (chemotherapy, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044971/" class="def">radiation therapy</a>, or <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046367/" class="def">hormonal therapy</a>) (n = 710) compared the outcomes of patients who received Iscador with patients who did not receive any added therapy. Patients who received Iscador developed significantly less adverse <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000348921/" class="def">drug</a> reactions associated with conventional treatment compared with women treated with conventional therapy alone (n = 732) (16% vs. 54.0%, respectively; adjusted <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000618610/" class="def">odds ratio</a> [OR], 0.47; 95% CI, 0.32–0.67; <i>P</i> < .001).[<a class="bibr" href="#CDR0000269596_rl_35_28" rid="CDR0000269596_rl_35_28">28</a>,<a class="bibr" href="#CDR0000269596_rl_35_29" rid="CDR0000269596_rl_35_29">29</a>] Relief or significant reductions in nausea, vomiting, loss of appetite, headache, fatigue, depression, skin and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000257213/" class="def">mucosal</a> reactions (including <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045789/" class="def">mucositis</a>), disturbed concentration and memory, and irritability were observed.[<a class="bibr" href="#CDR0000269596_rl_35_29" rid="CDR0000269596_rl_35_29">29</a>,<a class="bibr" href="#CDR0000269596_rl_35_30" rid="CDR0000269596_rl_35_30">30</a>] </p></div><div id="CDR0000269596__319"><h5>Head and neck cancers</h5><p id="CDR0000269596__320">After <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045570/" class="def">surgery</a> of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046056/" class="def">squamous cell</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046324/" class="def">lesions</a> of the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046026/" class="def">larynx</a> and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046061/" class="def">pharynx</a>, male patients who were randomly assigned to receive complementary IscadorQu treatment (n = 10) displayed significantly fewer <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044922/" class="def">adverse effects</a> from chemotherapy and radiation therapy (radiation therapy with 50–60 Gy, chemotherapy with cisplatin and fluorouracil) on the microcirculation and immunological capacities of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045993/" class="def">white blood cells</a> compared with men who received conventional treatment alone (n = 10) (<i>P</i> = .05).[<a class="bibr" href="#CDR0000269596_rl_35_31" rid="CDR0000269596_rl_35_31">31</a>] Patients who received adjuvant IscadorQu treatment also displayed significant accelerations in the restitution process when compared with the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044149/" class="def">control group</a> (<i>P</i> = .05).</p></div><div id="CDR0000269596__321"><h5>Non-small cell lung cancer (NSCLC) </h5><p id="CDR0000269596__322">Patients with advanced NSCLC who received carboplatin/gemcitabine or carboplatin/pemetrexed and were randomly assigned to receive open-label IscadorQu treatment (n = 33) displayed the following reactions when compared with patients who received chemotherapy alone (n = 39):[<a class="bibr" href="#CDR0000269596_rl_35_25" rid="CDR0000269596_rl_35_25">25</a>] </p><ul id="CDR0000269596__346"><li class="half_rhythm"><div>Significantly fewer hospitalizations (24% of Iscador-treated patients vs. 54% of control patients; <i>P</i> = .016).</div></li><li class="half_rhythm"><div>Chemotherapy dose reductions (13% of Iscador-treated patients vs. 44% of control patients; <i>P</i> = .005).</div></li><li class="half_rhythm"><div>Grades 3 and 4 nonhematological toxicities (16% of Iscador-treated patients vs. 41% of control patients; <i>P</i> = .043).</div></li></ul><p id="CDR0000269596__347">The grades 3 and 4 hematological <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000445093/" class="def">toxicity</a> was not significantly different between the groups.</p></div></div><div id="CDR0000269596__323"><h4>Survival</h4><div id="CDR0000269596__324"><h5>Miscellaneous cancers </h5><p id="CDR0000269596__325">A systematic review and meta-analysis of several studies published from 1963 to 2014, including RCTs, found that adjuvant treatment with Iscador is associated with improved cancer survival outcomes when compared with conventional treatment alone.[<a class="bibr" href="#CDR0000269596_rl_35_32" rid="CDR0000269596_rl_35_32">32</a>] Pooled analysis of controlled clinical studies (32 studies; total n = 13,745) that investigated <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000655245/" class="def">overall survival</a> (OS) and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000655269/" class="def">event-free survival</a> (EFS) (i.e., <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044023/" class="def">disease-free survival</a> [DFS], <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044782/" class="def">progression-free survival</a> [PFS] or <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000655254/" class="def">relapse-free survival</a>, or the time until these events occurred in cancer patients), demonstrates a statistically significant <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000618612/" class="def">hazard ratio</a> (HR) of 0.59 (95% CI, 0.53–0.65; <i>P</i> < .0001) in favor of Iscador treatment. A significant difference in survival between cancer types was noted (<i>P</i> < .01), with the strongest association of Iscador use and general survival found in in patients with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000444973/" class="def">cervical cancer</a> (HR, 0.43) and more modest outcomes in patients with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000445043/" class="def">lung cancer</a> (HR, 0.84). In the meta-analysis, randomization was performed in only 14 studies. While subgroup analysis displayed a greater association between EFS and OS in patients who received Iscador in nonrandomized clinical trials (HR, 0.56; CI, 0.50–0.62) compared with patients who were randomized (HR, 0.68; CI, 0.55–0.83); this difference is not statistically significant (<i>P</i> = .13).[<a class="bibr" href="#CDR0000269596_rl_35_32" rid="CDR0000269596_rl_35_32">32</a>] Many of the studies used study designs, analytical methods, and/or cancer treatment <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045864/" class="def">regimens</a> that were outdated. While moderate heterogeneity between study results was noted (I<sup>2</sup>, 50.9%; <i>P</i> < .0001), neither differences in design, sample size, nor publication year demonstrated significant effects on these survival outcomes. The reviewed studies were blinded; therefore, they ran the risk of performance <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044646/" class="def">bias</a>, given the knowledge of allocated interventions. It is unlikely that performance bias affected study outcomes associated with general survival (which is the reason why the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000454785/" class="def">U.S. Food and Drug Administration</a> does not mandate blinding in survival studies); however, performance bias may exist for those reporting on EFS.</p></div><div id="CDR0000269596__326"><h5>Breast cancer</h5><p id="CDR0000269596__327">Primary breast cancer patients (without <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045861/" class="def">recurrences</a>, lymphatic metastases, or <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000415317/" class="def">distant metastases</a> at the initiation of study <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045981/" class="def">observation</a>; n = 84 pairs) who received Iscador therapy adjuvant to conventional treatment (surgery, chemotherapy, radiation therapy, or hormone therapy) displayed prolonged cancer-specific <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044301/" class="def">survival rates</a> when matched to paired individuals with similar prognostic criteria who received conventional treatment alone (HR, 0.43; 95% CI, 0.27–0.68).[<a class="bibr" href="#CDR0000269596_rl_35_8" rid="CDR0000269596_rl_35_8">8</a>] In the same report, patients with breast cancer who were randomly assigned to receive Iscador did not demonstrate a significant extension of OS when compared with their matched pairs.[<a class="bibr" href="#CDR0000269596_rl_35_8" rid="CDR0000269596_rl_35_8">8</a>] </p><p id="CDR0000269596__328">In another study, OS was evaluated as a secondary endpoint in patients with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045805/" class="def">nonmetastatic</a> breast cancer (T2, 4N0, 2M0) who underwent adjuvant treatment <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000635464/" class="def">concomitant</a> with regimented Iscador <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044678/" class="def">injections</a>.[<a class="bibr" href="#CDR0000269596_rl_35_28" rid="CDR0000269596_rl_35_28">28</a>,<a class="bibr" href="#CDR0000269596_rl_35_29" rid="CDR0000269596_rl_35_29">29</a>] Women treated with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045914/" class="def">subcutaneous</a> Iscador therapy complementary to their conventional treatment regimen (n = 710) displayed significant extensions of overall <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000496502/" class="def">mortality</a> when compared with patients treated with conventional therapy alone (n = 732) (adjusted HR, 0.46; 95% CI, 0.22–0.96; <i>P</i> = .038).[<a class="bibr" href="#CDR0000269596_rl_35_28" rid="CDR0000269596_rl_35_28">28</a>,<a class="bibr" href="#CDR0000269596_rl_35_29" rid="CDR0000269596_rl_35_29">29</a>] </p></div><div id="CDR0000269596__329"><h5>Cervical cancer</h5><p id="CDR0000269596__330">Patients with metastatic (n = 66) or local (n = 102) cervical cancer who elected to receive Iscador in addition to conventional oncological treatment demonstrated significant extensions of OS when compared with women with similar prognostic criteria who received conventional treatment alone (HR and 95% CI, 0.37 [0.17–0.80] and 0.23 [0.14–0.39], respectively).[<a class="bibr" href="#CDR0000269596_rl_35_9" rid="CDR0000269596_rl_35_9">9</a>] However, this finding was not seen when women with metastatic cervical cancer were randomly assigned to receive open-label adjuvant Iscador.</p></div><div id="CDR0000269596__331"><h5>Colorectal cancer</h5><p id="CDR0000269596__332">Patients with surgically-treated, nonmetastatic <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000444983/" class="def">colorectal cancer</a> (CRC) (stages I–III) (n = 429) who received Iscador treatment with conventional aftercare displayed a statistically significant extension of DFS (HR, 0.60; <i>P</i> = .013) when compared with CRC patients who received conventional therapy alone (n = 375) after a median observation period of 58 months for patients who received Iscador and 51 months for patients who received conventional therapy alone.[<a class="bibr" href="#CDR0000269596_rl_35_33" rid="CDR0000269596_rl_35_33">33</a>] A secondary analysis of this data was preformed specific to CRC patients who received IscadorQu extract, a <i>Viscum album</i> extract harvested from oak (<i>Quercus</i>) trees. Patients who had specifically received IscadorQu extract (n = 106) displayed an estimated 69% risk reduction in metastasis formation (HR, 0.31; 95% CI, 0.13–0.711; <i>P</i> = .006) relative to conventionally-treated controls (n = 212).[<a class="bibr" href="#CDR0000269596_rl_35_34" rid="CDR0000269596_rl_35_34">34</a>]</p></div><div id="CDR0000269596__333"><h5>Melanoma </h5><p id="CDR0000269596__334">A <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045833/" class="def">phase III</a> study of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045135/" class="def">melanoma</a> patients (n = 102) with high-risk primary disease (stage II, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000681119/" class="def">Breslow thickness</a> >3mm) or <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044312/" class="def">regional lymph node</a> metastasis (stage III, after curative dissection) treated with IscadorM found no clinical benefit of low-dose <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045587/" class="def">adjuvant therapy</a> in the disease-free interval when compared with the control group (n = 102) after one year of treatment (or until <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045669/" class="def">tumor progression</a>).[<a class="bibr" href="#CDR0000269596_rl_35_5" rid="CDR0000269596_rl_35_5">5</a>]</p></div><div id="CDR0000269596__335"><h5>Non-small cell lung cancer (NSCLC)</h5><p id="CDR0000269596__336"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045762/" class="def">Lymph node</a>–positive NSCLC patients (n = 87) who were randomly assigned to receive Iscador therapy (without concurrent treatment) displayed significant extensions in <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000655249/" class="def">median survival</a> rates when compared with untreated controls.[<a class="bibr" href="#CDR0000269596_rl_35_35" rid="CDR0000269596_rl_35_35">35</a>] Clinical benefit in median survival was not observed in patients with nonmetastatic NSCLC.[<a class="bibr" href="#CDR0000269596_rl_35_35" rid="CDR0000269596_rl_35_35">35</a>] Similarly, a three-arm comparison with a sheep <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046593/" class="def">spleen</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285966/" class="def">glycopeptide</a>, reported to be an <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285968/" class="def">immunostimulant</a> and an inhibitor of tumor <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046476/" class="def">cell</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044131/" class="def">glycolysis</a>, and a vitamin B preparation (<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046688/" class="def">placebo</a>) (n = 107), found no clinical benefit in median survival above placebo in patients with advanced NSCLC who were randomly assigned to receive IscadorQu and IscadorU (n = 105) after two years of open-label treatment.[<a class="bibr" href="#CDR0000269596_rl_35_26" rid="CDR0000269596_rl_35_26">26</a>]</p></div><div id="CDR0000269596__337"><h5>Osteosarcoma</h5><p id="CDR0000269596__338">Osteosarcoma patients who underwent a complete surgical resection after a second relapse were randomly assigned to receive IscadorP <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045768/" class="def">maintenance therapy</a> (subcutaneous injections three times a week) (n = 9) for 1 year. After a <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044671/" class="def">follow-up</a> period of 12 years, patients displayed a 71% reduced risk of relapse (measured as postrelapse DFS; HR, 0.287; 95% CI, 0.076–0.884; <i>P</i> = .03) when compared with patients who received 6 months of oral etoposide treatment (50 <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044213/" class="def">mg</a>/m<sup>2</sup> a day for 21 days, every 28 days) (n = 10).[<a class="bibr" href="#CDR0000269596_rl_35_36" rid="CDR0000269596_rl_35_36">36</a>]</p></div><div id="CDR0000269596__339"><h5>Ovarian cancer </h5><p id="CDR0000269596__340">Primary ovarian cancer patients without distant metastases (n = 21 pairs) who received Iscador therapy after conventional treatment (surgery and chemotherapy) displayed prolonged OS rates when compared with patients with similar prognostic criteria who received conventional treatment alone (HR, 0.47; 95% CI, 0.31–0.69; <i>P</i> = .0002).[<a class="bibr" href="#CDR0000269596_rl_35_11" rid="CDR0000269596_rl_35_11">11</a>] Patients who were randomized to receive Iscador treatment did not display a significant difference in OS when compared with matched controls. Patients with metastatic ovarian cancer, randomly assigned to receive complementary Iscador therapy (n = 20 pairs), also demonstrated a significant extension of OS when compared with matched pairs (HR, 0.33; 95% CI, 0.12–0.92; <i>P</i> = .033), although a significant extension in OS was not observed in the nonrandomized arm.[<a class="bibr" href="#CDR0000269596_rl_35_11" rid="CDR0000269596_rl_35_11">11</a>]</p></div><div id="CDR0000269596__341"><h5>Pancreatic cancer </h5><p id="CDR0000269596__342">Patients with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045955/" class="def">locally advanced</a> or metastatic <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044521/" class="def">pancreatic cancer</a> (UICC stage III or stage IV) who were randomly assigned to receive open-label Iscador therapy as an adjuvant to <i>best supportive care</i> methods (n = 110) demonstrated prolonged survival when compared with patients under similar prognostic criteria who received supportive care alone (n = 110). The median OS was 4.8 months for patients who received Iscador and 2.2 months for patients who received supportive care alone (prognosis-adjusted HR, 0.49; 95% CI, 0.36–0.65; <i>P</i> < .0001).[<a class="bibr" href="#CDR0000269596_rl_35_37" rid="CDR0000269596_rl_35_37">37</a>] </p><p id="CDR0000269596__482">A <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044120/" class="def">retrospective</a> analysis investigated the effects of mistletoe and chemotherapy with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000468790/" class="def">hyperthermia</a> versus mistletoe and chemotherapy in the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045815/" class="def">palliative treatment</a> of patients with pancreatic cancer. The results of the analysis found a significant improvement in survival rates for patients who received all three treatments. Weaknesses of the analysis include the retrospective nature of the study, multiple types of chemotherapy (gemcitabine/nab-<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045258/" class="def">paclitaxel</a>, 34%; <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000711871/" class="def">FOLFIRINOX</a>, 36%; gemcitabine, 30%) and mistletoe (e.g., Iscador, Abnoba viscum, or Helixor) regimens used, and the lack of a study arm for hyperthermia and chemotherapy.[<a class="bibr" href="#CDR0000269596_rl_35_38" rid="CDR0000269596_rl_35_38">38</a>] Furthermore, the study was not stratified despite enrolling patients who were previously treated with 1 to 3 lines of therapy, making the group median survival rates clinically insignificant.</p><p id="CDR0000269596__343">In a retrospective analysis of patients with stages I to IV pancreatic cancer (n = 292) who received Iscador (host tree unspecified) therapy alone or adjuvant to conventional treatment (surgery, chemotherapy, radiation therapy, hormone therapy, or a combination) (n = 61), a median survival of 6.58 months was reported.[<a class="bibr" href="#CDR0000269596_rl_35_39" rid="CDR0000269596_rl_35_39">39</a>]</p></div><div id="CDR0000269596__344"><h5>Uterine cancer </h5><p id="CDR0000269596__345">Patients with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046456/" class="def">corpus uteri</a> cancer without distant metastases (n = 30 pairs) were randomly assigned to receive Iscador therapy adjuvant to conventional treatment (surgery or radiation therapy). Patients had longer OS (time from initial <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046450/" class="def">diagnosis</a> to tumor-related death) than matched pairs of patients with similar prognostic criteria who received conventional treatment alone (HR, 0.36; 95% CI, 0.16–0.82; <i>P</i> = .014).[<a class="bibr" href="#CDR0000269596_rl_35_10" rid="CDR0000269596_rl_35_10">10</a>] However, corpus uteri cancer patients with distant metastases randomly assigned to receive adjuvant Iscador did not display a significant difference in OS when compared with matched controls who were randomly assigned to conventional oncologic care only. In the nonrandomized portion of the study, corpus uteri cancer patients, with (n = 95 pairs) or without (n = 103 pairs) distant metastases, who previously received the complementary therapy, demonstrated a significant extension of OS when compared with matched pairs of similar prognostic criteria who received conventional treatment alone (prognosis-adjusted HR and 95% CI, 0.61 [0.39–0.93], <i>P</i> = .023 and 0.41 [0.26–0.63], <i>P</i> < .0001, respectively).[<a class="bibr" href="#CDR0000269596_rl_35_10" rid="CDR0000269596_rl_35_10">10</a>]</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figCDR0000269596194"><a href="/books/NBK66054/table/CDR0000269596__194/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobCDR0000269596194"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="CDR0000269596__194"><a href="/books/NBK66054/table/CDR0000269596__194/?report=objectonly" target="object" rid-ob="figobCDR0000269596194">Table</a></h4><p class="float-caption no_bottom_margin">Table 3. Use of Iscador in Cancer Treatment: Clinical Reports Describing Therapeutic End Points<sup>a</sup>. </p></div></div></div></div></div><div id="CDR0000269596__126"><h3>Helixor</h3><div id="CDR0000269596__478"><h4>Safety</h4><p id="CDR0000269596__479">The first <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046682/" class="def">intravenous</a> (IV) trial of mistletoe (HelixorM) is completed.[<a class="bibr" href="#CDR0000269596_rl_35_42" rid="CDR0000269596_rl_35_42">42</a>] A standard 3 + 3 <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045830/" class="def">phase I</a> design was used. The study included 21 patients with heavily pretreated metastatic <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045301/" class="def">solid tumors</a>. A dose of 600 mg IV 3 times a week was determined to be the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000546597/" class="def">maximum tolerated dose</a> recommended for future <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045831/" class="def">phase II</a> trials. Three patients had tumor shrinkage, though none met <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000691009/" class="def">RECIST</a> criteria for a <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045819/" class="def">partial response</a>. The disease control rate was 23.8% and the median <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045884/" class="def">stable disease</a> was 15 weeks. Two patients had stable disease for almost 6 months. The most common treatment-related adverse events were fatigue (28.6%), nausea (9.5%), and chills (9.5%). A secondary endpoint analysis found that QOL was significantly improved during treatment as measured by the Functional Assessment of Cancer Therapy-General assessment, with a change in score from 79.7 to 93 between week 1 and week 4.[<a class="bibr" href="#CDR0000269596_rl_35_42" rid="CDR0000269596_rl_35_42">42</a>] Future research should be conducted to examine the effect of mistletoe on chemotherapy tolerability and to gather more information about its effect on QOL, PFS, and OS.</p></div><div id="CDR0000269596__417"><h4>Quality of life</h4><div id="CDR0000269596__418"><h5>Miscellaneous cancers</h5><p id="CDR0000269596__419">Patients with cancer (breast, n = 67; ovarian, n = 66; NSCLC, n = 91) were randomly assigned to receive open-label treatment with HelixorA (<i>viscum album</i> abietis) concurrent with standard chemotherapy (n = 115). These patients demonstrated significant improvements in QOL (as assessed by Functional Living Index-Cancer, Karnofsky Performance Index, and Traditional Chinese Medicine Index questionnaires) when compared with patients in the control group, who received conventional oncologic treatment and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044157/" class="def">Lentinan</a>, an <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000739791/" class="def">immunomodulating agent</a> derived from the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285741/" class="def">shiitake mushroom</a> (n = 109) (<i>P</i> < .05).[<a class="bibr" href="#CDR0000269596_rl_35_43" rid="CDR0000269596_rl_35_43">43</a>] Patients who received HelixorA also experienced fewer adverse events (AEs) from chemotherapy when compared with the control group (52 AEs reported in the HelixorA and chemotherapy group vs. 90 AEs in the control group).</p></div></div><div id="CDR0000269596__420"><h4>Symptom management </h4><div id="CDR0000269596__421"><h5>Malignant pleural effusion</h5><p id="CDR0000269596__422"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044294/" class="def">Pleurodesis</a> with HelixorM (<i>Viscum album</i> mali) may be an effective procedure to control <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000524207/" class="def">malignant pleural effusions</a> (MPE) in patients with advanced lung cancer.[<a class="bibr" href="#CDR0000269596_rl_35_44" rid="CDR0000269596_rl_35_44">44</a>] Over half (52%) of lung cancer patients treated with HelixorM pleurodesis (n = 42) were free from recurrence of MPE one month after the procedure. Neither patient characteristics (including age, gender, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000467841/" class="def">histopathology</a>, or <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045922/" class="def">systemic treatment</a>), nor MPE characteristics (including location and chemistry) was deemed significantly associated with the outcome of HelixorM pleurodesis in this study.[<a class="bibr" href="#CDR0000269596_rl_35_44" rid="CDR0000269596_rl_35_44">44</a>]</p></div></div><div id="CDR0000269596__423"><h4>Survival</h4><div id="CDR0000269596__424"><h5>Breast cancer</h5><p id="CDR0000269596__425">Patients with breast cancer (T1–3, N0–3, M0; <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000559442/" class="def">local recurrence</a>) were randomly assigned to receive Helixor adjuvant to conventional therapy (i.e., surgery and radiation therapy) (n = 192). These patients demonstrated a significant extension in 5-year survival when compared with patients who received conventional treatment alone (n = 274) (5-year survival rates, 69.1% vs. 59.7%, respectively) (<i>P</i> = .048).[<a class="bibr" href="#CDR0000269596_rl_35_45" rid="CDR0000269596_rl_35_45">45</a>]</p></div><div id="CDR0000269596__426"><h5>Colorectal cancer </h5><p id="CDR0000269596__427">Patients with metastatic CRC were randomly assigned to receive Helixor adjuvant to chemotherapy (n = 20). These patients demonstrated significant extensions in mean survival (26.7 ± 11.9 months in complete/partial responders) when compared with patients randomly assigned to receive chemotherapy alone (n = 20) (13.6 ± 4.4 months in complete/partial responders).[<a class="bibr" href="#CDR0000269596_rl_35_46" rid="CDR0000269596_rl_35_46">46</a>]</p></div></div></div><div id="CDR0000269596__428"><h3>abnobaVISCUM</h3><div id="CDR0000269596__429"><h4>Quality of life</h4><div id="CDR0000269596__430"><h5>Breast cancer</h5><p id="CDR0000269596__431">As per QLQ-C30 function scales, health-related QOL in patients with breast cancer (stages I–III) who received abnobaVISCUMM concurrent with chemotherapy (n = 270) remained stable throughout the course of chemotherapy and significantly improved 4 weeks after treatment (<i>P</i> < .0001) when compared with the initial visit.[<a class="bibr" href="#CDR0000269596_rl_35_47" rid="CDR0000269596_rl_35_47">47</a>] Patients also showed significant improvements above baseline in all parameters of the QLQ-BR23 function scale (a QOL module specific to breast cancer) at final examination (<i>P</i> < .0001).</p></div><div id="CDR0000269596__432"><h5>Stomach cancer</h5><p id="CDR0000269596__433">Postoperative patients with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000454513/" class="def">gastric cancer</a> (stage IB or stage II) were randomly assigned to receive abnobaVISCUMQ adjuvant to <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000689103/" class="def">oral chemotherapy</a> (n = 15). These patients demonstrated a significant improvement in <i>global health status</i> (a parameter constructed by totaling scores on two questions from the QLQ-C30 questionnaire) at week 16 and at completion of treatment (week 24), when compared with patients who received oral chemotherapy alone (n = 14) (<i>P</i> = .0098).[<a class="bibr" href="#CDR0000269596_rl_35_48" rid="CDR0000269596_rl_35_48">48</a>] All other function and symptom scales of the QLQ-C30 and the QLQ-STO22 (a QOL module specific to stomach cancer) did not show statistical significance when abnobaVISCUMQ treatment was added.[<a class="bibr" href="#CDR0000269596_rl_35_48" rid="CDR0000269596_rl_35_48">48</a>]</p></div></div><div id="CDR0000269596__434"><h4>Symptom management </h4><div id="CDR0000269596__435"><h5>Miscellaneous cancers</h5><p id="CDR0000269596__436">Patients with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000478743/" class="def">advanced cancer</a> were treated with abnobaVISCUM pleurodesis for MPE (n = 62). These patients demonstrated a significant improvement in mean <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000043983/" class="def">response rate</a> (<i>P</i> < .0001) when compared with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000635451/" class="def">reference values</a> (97% and 64%, respectively).[<a class="bibr" href="#CDR0000269596_rl_35_49" rid="CDR0000269596_rl_35_49">49</a>] Forty-nine patients (79%) demonstrated a <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045652/" class="def">complete response</a> (no recurrence of MPE at least 4 weeks after treatment) and 11 patients (18%) demonstrated partial response (reaccumulation of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045843/" class="def">pleural effusion</a> under 50% of the pretreatment volume), while 2 patients (3.23%) did not respond (recurrence of pleural effusion within 4 weeks after treatment) to mistletoe-mediated pleurodesis with abnobaVISCUM.[<a class="bibr" href="#CDR0000269596_rl_35_49" rid="CDR0000269596_rl_35_49">49</a>]</p></div><div id="CDR0000269596__437"><h5>Colorectal cancer </h5><p id="CDR0000269596__438"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044090/" class="def">Symptomatic</a> relief was reported by 40% of patients with metastatic CRC who were resistant to fluorouracil and leucovorin (5-FU/LV)-based chemotherapy and received abnobaVISCUMQ therapy (n = 25). Symptomatic relief was assessed as a secondary endpoint measure for a median duration of 14 weeks.[<a class="bibr" href="#CDR0000269596_rl_35_50" rid="CDR0000269596_rl_35_50">50</a>] Relief of the following symptoms was reported:</p><ul id="CDR0000269596__439"><li class="half_rhythm"><div>Nausea and vomiting (24% of patients).</div></li><li class="half_rhythm"><div>Diarrhea (12% of patients).</div></li><li class="half_rhythm"><div><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000407757/" class="def">Constipation</a> (8% of patients).</div></li><li class="half_rhythm"><div>Fatigue (24% of patients).</div></li><li class="half_rhythm"><div>Dyspnea (8% of patients).</div></li></ul></div><div id="CDR0000269596__440"><h5>Stomach cancer</h5><p id="CDR0000269596__441">In one study, postoperative patients with gastric cancer (stage IB or stage II) were randomly assigned to receive abnobaVISCUMQ adjuvant to oral chemotherapy (n = 15). The secondary endpoint analyses demonstrated a significant improvement in <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046067/" class="def">leukocyte</a> (<i>P</i> = .01) and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044844/" class="def">eosinophil</a> (<i>P</i> = .0036) counts when compared with patients who received oral chemotherapy alone (n = 14) after a 24-week <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000688840/" class="def">treatment cycle</a>.[<a class="bibr" href="#CDR0000269596_rl_35_48" rid="CDR0000269596_rl_35_48">48</a>]</p></div></div><div id="CDR0000269596__442"><h4>Survival</h4><div id="CDR0000269596__443"><h5>Bladder cancer</h5><p id="CDR0000269596__444">A marker tumor <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045867/" class="def">remission</a> rate of 55.6% (95% CI, 38.1–72.1) was achieved in 20 of 36 patients with nonmuscle-invasive bladder cancer (Ta G1/G2 or T1 G1/G2) 12 weeks after beginning bladder <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285971/" class="def">instillation</a> therapy with abnobaVISCUMF (once a week for 6 weeks).[<a class="bibr" href="#CDR0000269596_rl_35_51" rid="CDR0000269596_rl_35_51">51</a>] Of the 19 evaluable patients, 14 (73.7%) did not have recurrent tumor at 1 year after initiation of treatment (95% CI, 48.8%–90.9%), corresponding to a 1-year recurrence rate of 26.3% (95% CI, 9.1%–51.2%).</p></div><div id="CDR0000269596__445"><h5>Colorectal cancer</h5><p id="CDR0000269596__446">Objective tumor response was not observed in a phase II study of patients with metastatic CRC who were resistant to 5-FU/LV-based chemotherapy and received abnobaVISCUMQ therapy for a median time period of 14 weeks. Stable disease was noted in 21 of 25 patients (84%), lasting for a median of 2.5 months (range; 1.5–7 months).[<a class="bibr" href="#CDR0000269596_rl_35_50" rid="CDR0000269596_rl_35_50">50</a>]</p></div></div></div><div id="CDR0000269596__447"><h3>Eurixor</h3><p id="CDR0000269596__448">Eurixor is no longer available on the market for sale.</p><div id="CDR0000269596__449"><h4>Quality of life</h4><div id="CDR0000269596__450"><h5>Colorectal cancer</h5><p id="CDR0000269596__451">Patients with metastatic CRC were randomly assigned to receive Eurixor adjuvant to standard cancer treatment (n = 38). These patients demonstrated improved QOL (<i>P</i> = .0001) when compared with patients randomly assigned to receive standard treatment alone (n = 41).[<a class="bibr" href="#CDR0000269596_rl_35_52" rid="CDR0000269596_rl_35_52">52</a>,<a class="bibr" href="#CDR0000269596_rl_35_53" rid="CDR0000269596_rl_35_53">53</a>]</p></div></div><div id="CDR0000269596__452"><h4>Symptom management</h4><div id="CDR0000269596__453"><h5>Breast cancer</h5><p id="CDR0000269596__454">Patients with breast cancer (UICC stages I–IIIB) underwent postoperative chemotherapy, radiation therapy, or hormone therapy, and received complementary treatment with Eurixor (n = 219) for a median time period of 270 days. These patients demonstrated significant improvements in disease- or therapy-induced adverse reactions (<i>P</i> < .0001) when compared with patients who received standard cancer therapy alone (n = 470) at up to 285 days of follow-up.[<a class="bibr" href="#CDR0000269596_rl_35_54" rid="CDR0000269596_rl_35_54">54</a>] Significant improvements in nausea, appetite reduction, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046604/" class="def">stomach</a> pain, fatigue, depression, memory, and irritability/restlessness were reported (<i>P</i> < .0001, in each subgroup).</p></div></div><div id="CDR0000269596__455"><h4>Survival</h4><div id="CDR0000269596__456"><h5>Bladder cancer</h5><p id="CDR0000269596__457">Patients with bladder cancer (pTa G1/G2) (n = 45) received subcutaneous Eurixor injections after <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045971/" class="def">transurethral resection</a>. These patients did not demonstrate differences in time-to-first recurrence, total number of recurrences, or recurrence-free outcomes at up to 18 months after <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000589417/" class="def">primary treatment</a> compared with patients who were randomly assigned to receive no adjuvant treatment.[<a class="bibr" href="#CDR0000269596_rl_35_3" rid="CDR0000269596_rl_35_3">3</a>]</p></div><div id="CDR0000269596__458"><h5>Head and neck cancers</h5><p id="CDR0000269596__459">Patients treated with Eurixor before and after resection of squamous cell carcinomas of the head and neck, with or without follow-up radiation therapy, demonstrated no difference in DFS when compared with patients who received surgery alone or surgery followed by radiation therapy, without adjuvant Eurixor treatment.[<a class="bibr" href="#CDR0000269596_rl_35_2" rid="CDR0000269596_rl_35_2">2</a>]</p></div></div></div><div id="CDR0000269596__460"><h3>Isorel</h3><p id="CDR0000269596__461">Isorel is no longer available on the market for sale.</p><div id="CDR0000269596__462"><h4>Biomarker study</h4><div id="CDR0000269596__463"><h5>Gastrointestinal cancers</h5><p id="CDR0000269596__464"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044076/" class="def">Perioperative</a> use of Isorel in patients with cancer of the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046447/" class="def">digestive tract</a> (<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046414/" class="def">esophageal</a>, stomach, pancreatic, ileac, colorectal) has been shown to increase the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045765/" class="def">lymphocyte</a> count in patients within 14 days of administration.[<a class="bibr" href="#CDR0000269596_rl_35_55" rid="CDR0000269596_rl_35_55">55</a>]</p></div></div><div id="CDR0000269596__465"><h4>Survival</h4><div id="CDR0000269596__466"><h5>Colorectal cancer</h5><p id="CDR0000269596__467">Patients with advanced CRC (Dukes C and D) were randomly assigned to receive Isorel along with adjuvant postoperative chemotherapy with 5-FU (6 cycles) (n = 29). These patients demonstrated prolonged survival (<i>P</i> < .05) when compared with patients who received postoperative chemotherapy only (n = 21) and patients who received surgery only (n = 14) without postoperative chemotherapy or Isorel treatment (n = 14).[<a class="bibr" href="#CDR0000269596_rl_35_56" rid="CDR0000269596_rl_35_56">56</a>]</p></div></div></div><div id="CDR0000269596__468"><h3>Lektin/Lektinol</h3><div id="CDR0000269596__469"><h4>Quality of life</h4><div id="CDR0000269596__470"><h5>Breast cancer</h5><p id="CDR0000269596__471">Patients with breast cancer were randomly assigned to receive open-label PS76A (an <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000043998/" class="def">aqueous</a> mistletoe extract standardized to the galactoside-specific <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044994/" class="def">mistletoe lectin</a> [ML]) adjuvant to chemotherapy (n = 176). These patients demonstrated improved QOL when compared with patients who received chemotherapy alone.[<a class="bibr" href="#CDR0000269596_rl_35_13" rid="CDR0000269596_rl_35_13">13</a>]</p><p id="CDR0000269596__472">In a <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045673/" class="def">double-blind study</a>, patients with breast cancer (stages II–III) were randomly assigned to receive PS76A2 (Lektinol; 30 ng ML/mL) adjuvant to cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy (4 cycles) for a period of 15 consecutive weeks (n = 65). These patients demonstrated statistically significant improvements in self-assessments of QOL (<i>P</i> = .0121 and <i>P</i> = .0021 for GLQ-8 and Spitzer’s uniscale, respectively) when compared with patients who were randomly assigned to receive chemotherapy treatment alone (n = 66).[<a class="bibr" href="#CDR0000269596_rl_35_57" rid="CDR0000269596_rl_35_57">57</a>] Only the medium dose (30 ng ML/mL) indicated a significant preventative effect against placebo; no treatment effect of low- or high-dose Lektinol (10 ng ML/mL or 70 ng ML/mL) was established against the placebo. In a second confirmatory study, superiority of complementary Lektinol (30 ng ML/mL) (n = 176) over the placebo (n = 176) was observed according to three FACT-G subscales (physical, emotional, and functional well-being) assessed during the fourth CMF cycle (<i>P</i> < .0001).[<a class="bibr" href="#CDR0000269596_rl_35_58" rid="CDR0000269596_rl_35_58">58</a>]</p></div></div></div><div id="CDR0000269596__407"><h3>Systematic Reviews/Meta-analyses of Various <i>Viscum Album</i> Extract (VAE) Types</h3><div id="CDR0000269596__408"><h4>Quality of life</h4><div id="CDR0000269596__409"><h5>Miscellaneous cancers</h5><p id="CDR0000269596__410">Some systematic reviews have found that studies of better methodological quality typically show that <i>Viscum album</i> extracts (VAEs) have few beneficial effects on QOL in cancer,[<a class="bibr" href="#CDR0000269596_rl_35_18" rid="CDR0000269596_rl_35_18">18</a>,<a class="bibr" href="#CDR0000269596_rl_35_20" rid="CDR0000269596_rl_35_20">20</a>,<a class="bibr" href="#CDR0000269596_rl_35_59" rid="CDR0000269596_rl_35_59">59</a>] while others studies suggest that mistletoe extracts produce a significant, though medium-sized, effect on QOL in cancer patients (mean difference = 0.61; 95% CI, 0.41–0.81, <i>P</i> < .00001).[<a class="bibr" href="#CDR0000269596_rl_35_60" rid="CDR0000269596_rl_35_60">60</a>]</p><p id="CDR0000269596__411">However, another systematic review reached different conclusions. In a review consisting of 26 RCTs, 22 reported a benefit of mistletoe therapy (supplied with or without concomitant surgery, chemotherapy, or radiation therapy), whereas 3 reported no difference, and 1 did not indicate a result.[<a class="bibr" href="#CDR0000269596_rl_35_22" rid="CDR0000269596_rl_35_22">22</a>] All 10 nonRCTs reported a benefit of VAE treatment, whether it was supplied with or without concomitant therapy.[<a class="bibr" href="#CDR0000269596_rl_35_22" rid="CDR0000269596_rl_35_22">22</a>] Among the studies designated as higher in methodological quality, most reported a benefit of VAE treatment, whereas one reported no difference from standard oncological treatment. Most consistently, studies reported improvements regarding the following:[<a class="bibr" href="#CDR0000269596_rl_35_22" rid="CDR0000269596_rl_35_22">22</a>]</p><ul id="CDR0000269596__412"><li class="half_rhythm"><div> Coping.</div></li><li class="half_rhythm"><div>Fatigue.</div></li><li class="half_rhythm"><div>Sleep.</div></li><li class="half_rhythm"><div>Exhaustion.</div></li><li class="half_rhythm"><div>Energy.</div></li><li class="half_rhythm"><div>Nausea.</div></li><li class="half_rhythm"><div>Vomiting.</div></li><li class="half_rhythm"><div>Appetite.</div></li><li class="half_rhythm"><div>Depression.</div></li><li class="half_rhythm"><div><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000430405/" class="def">Anxiety</a>.</div></li><li class="half_rhythm"><div>Ability to work.</div></li><li class="half_rhythm"><div>Emotional and functional well-being.</div></li></ul></div></div><div id="CDR0000269596__413"><h4>Survival</h4><div id="CDR0000269596__414"><h5>Miscellaneous cancers</h5><p id="CDR0000269596__415">Systematic reviews reported inconsistent results regarding the efficacy of mistletoe treatment on survival outcomes on the basis of methodological quality of the study.[<a class="bibr" href="#CDR0000269596_rl_35_61" rid="CDR0000269596_rl_35_61">61</a>] In a review that consisted of 28 publications (n = 2,639) investigating a wide range of cancers (bladder, breast, cervix, lungs, uterus, ovaries, colon, stomach, pancreas, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045700/" class="def">gliomas</a>, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000257519/" class="def">head and neck cancers</a>, melanomas, and osteosarcomas), most studies did not show that adjuvant mistletoe had an effect on survival, especially those of high methodological quality.[<a class="bibr" href="#CDR0000269596_rl_35_62" rid="CDR0000269596_rl_35_62">62</a>] This finding is consistent with other review articles. In an investigation of 13 RCTs, 6 showed evidence of a survival benefit, but none of these studies were of high methodological quality.[<a class="bibr" href="#CDR0000269596_rl_35_18" rid="CDR0000269596_rl_35_18">18</a>]</p><p id="CDR0000269596__416">In another review of 23 controlled clinical studies (16 randomized, 2 quasi-randomized, and 5 nonrandomized) that investigated the use of VAE in patients with cancers of the breast, lung, stomach, colon, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046555/" class="def">rectum</a>, head and neck, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046325/" class="def">kidney</a>, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000476624/" class="def">genitals</a>, bladder, melanomas, and gliomas, positive effects on survival were indicated in 8 studies and tumor remission was supported by 1 study.[<a class="bibr" href="#CDR0000269596_rl_35_16" rid="CDR0000269596_rl_35_16">16</a>] Four studies reported no effect on survival, one indicated no effect on DFS, two reported no benefit of treatment on tumor recurrence, and three indicated no effect on cancer remission.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figCDR000026959671"><a href="/books/NBK66054/table/CDR0000269596__71/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobCDR000026959671"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="CDR0000269596__71"><a href="/books/NBK66054/table/CDR0000269596__71/?report=objectonly" target="object" rid-ob="figobCDR000026959671">Table</a></h4><p class="float-caption no_bottom_margin">Table 4. Use of Other Mistletoe Products in Cancer Treatment: Clinical Reports Describing Therapeutic End Points<sup>a</sup>. </p></div></div></div></div></div><div id="CDR0000269596__TrialSearch_35_sid_5"><h3>Current Clinical Trials</h3><p id="CDR0000269596__TrialSearch_35_22">Use our <a href="https://www.cancer.gov/research/participate/clinical-trials-search/advanced" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">advanced clinical trial search</a> to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. <a href="https://www.cancer.gov/research/participate/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General information</a> about clinical trials is also available.</p></div><div id="CDR0000269596_rl_35"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000269596_rl_35_1">Lenartz D, Dott U, Menzel J, et al.: Survival of glioma patients after complementary treatment with galactoside-specific lectin from mistletoe. Anticancer Res 20 (3B): 2073-6, 2000 May-Jun. [<a href="https://pubmed.ncbi.nlm.nih.gov/10928154" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10928154</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_35_2">Steuer-Vogt MK, Bonkowsky V, Ambrosch P, et al.: The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial. Eur J Cancer 37 (1): 23-31, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11165126" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11165126</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_35_3">Goebell PJ, Otto T, Suhr J, et al.: Evaluation of an unconventional treatment modality with mistletoe lectin to prevent recurrence of superficial bladder cancer: a randomized phase II trial. J Urol 168 (1): 72-5, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/12050495" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12050495</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_35_4">Grossarth-Maticek R, Kiene H, Baumgartner SM, et al.: Use of Iscador, an extract of European mistletoe (Viscum album), in cancer treatment: prospective nonrandomized and randomized matched-pair studies nested within a cohort study. Altern Ther Health Med 7 (3): 57-66, 68-72, 74-6 passim, 2001 May-Jun. [<a href="https://pubmed.ncbi.nlm.nih.gov/11347286" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11347286</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_35_5">Kleeberg UR, Suciu S, Bröcker EB, et al.: Final results of the EORTC 18871/DKG 80-1 randomised phase III trial. rIFN-alpha2b versus rIFN-gamma versus ISCADOR M versus observation after surgery in melanoma patients with either high-risk primary (thickness >3 mm) or regional lymph node metastasis. Eur J Cancer 40 (3): 390-402, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/14746858" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14746858</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_35_6">Viscum album. In: Homoeopathic Pharmacopoeia Convention of the United States: Homoeopathic Pharmacopoeia of the United States. 2002, Monograph 9444 Visc.</div></li><li><div class="bk_ref" id="CDR0000269596_rl_35_7">Tröger W, Jezdić S, Ždrale Z, et al.: Quality of life and neutropenia in patients with early stage breast cancer: a randomized pilot study comparing additional treatment with mistletoe extract to chemotherapy alone
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. Breast Cancer: Basic and Clinical Research 3: 35-45, 2009. [<a href="/pmc/articles/PMC3086310/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3086310</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21556248" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21556248</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_35_8">Grossarth-Maticek R, Ziegler R: Prospective controlled cohort studies on long-term therapy of breast cancer patients with a mistletoe preparation (Iscador). Forsch Komplementmed 13 (5): 285-92, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/17057389" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17057389</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_35_9">Grossarth-Maticek R, Ziegler R: Prospective controlled cohort studies on long-term therapy of cervical cancer patients with a mistletoe preparation (Iscador). Forsch Komplementmed 14 (3): 140-7, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17596694" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17596694</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_35_10">Grossarth-Maticek R, Ziegler R: Randomized and non-randomized prospective controlled cohort studies in matched pair design for the long-term therapy of corpus uteri cancer patients with a mistletoe preparation (Iscador). Eur J Med Res 13 (3): 107-20, 2008. 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Anticancer Res 25 (6C): 4583-90, 2005 Nov-Dec. [<a href="https://pubmed.ncbi.nlm.nih.gov/16334146" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16334146</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_35_56">Cazacu M, Oniu T, Lungoci C, et al.: The influence of isorel on the advanced colorectal cancer. Cancer Biother Radiopharm 18 (1): 27-34, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/12667306" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12667306</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_35_57">Semiglasov VF, Stepula VV, Dudov A, et al.: The standardised mistletoe extract PS76A2 improves QoL in patients with breast cancer receiving adjuvant CMF chemotherapy: a randomised, placebo-controlled, double-blind, multicentre clinical trial. Anticancer Res 24 (2C): 1293-302, 2004 Mar-Apr. [<a href="https://pubmed.ncbi.nlm.nih.gov/15154663" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15154663</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_35_58">Semiglazov VF, Stepula VV, Dudov A, et al.: Quality of life is improved in breast cancer patients by Standardised Mistletoe Extract PS76A2 during chemotherapy and follow-up: a randomised, placebo-controlled, double-blind, multicentre clinical trial. Anticancer Res 26 (2B): 1519-29, 2006 Mar-Apr. [<a href="https://pubmed.ncbi.nlm.nih.gov/16619567" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16619567</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_35_59">Freuding M, Keinki C, Kutschan S, et al.: Mistletoe in oncological treatment: a systematic review : Part 2: quality of life and toxicity of cancer treatment. J Cancer Res Clin Oncol 145 (4): 927-939, 2019. [<a href="https://pubmed.ncbi.nlm.nih.gov/30673872" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30673872</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_35_60">Loef M, Walach H: Quality of life in cancer patients treated with mistletoe: a systematic review and meta-analysis. BMC Complement Med Ther 20 (1): 227, 2020. [<a href="/pmc/articles/PMC7370416/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7370416</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32690087" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32690087</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_35_61">Melzer J, Iten F, Hostanska K, et al.: Efficacy and safety of mistletoe preparations (Viscum album) for patients with cancer diseases. A systematic review. Forsch Komplementmed 16 (4): 217-26, 2009. [<a href="https://pubmed.ncbi.nlm.nih.gov/19729932" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19729932</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_35_62">Freuding M, Keinki C, Micke O, et al.: Mistletoe in oncological treatment: a systematic review : Part 1: survival and safety. J Cancer Res Clin Oncol 145 (3): 695-707, 2019. [<a href="https://pubmed.ncbi.nlm.nih.gov/30673873" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30673873</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_35_63">Lenartz D, Stoffel B, Menzel J, et al.: Immunoprotective activity of the galactoside-specific lectin from mistletoe after tumor destructive therapy in glioma patients. Anticancer Res 16 (6B): 3799-802, 1996 Nov-Dec. [<a href="https://pubmed.ncbi.nlm.nih.gov/9042260" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9042260</span></a>]</div></li></ol></div></div><div id="CDR0000269596__52"><h2 id="_CDR0000269596__52_">Adverse Effects</h2><p id="CDR0000269596__53">Although a number of different <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285939/" class="def">mistletoe</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000407760/" class="def">extracts</a> have been used in <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044195/" class="def">human studies</a>, the reported <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046580/" class="def">side effects</a> have generally been minimal and not life threatening. Common side effects include the following:[<a class="bibr" href="#CDR0000269596_rl_52_1" rid="CDR0000269596_rl_52_1">1</a>-<a class="bibr" href="#CDR0000269596_rl_52_4" rid="CDR0000269596_rl_52_4">4</a>]</p><ul id="CDR0000269596__291"><li class="half_rhythm"><div>Soreness and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044042/" class="def">inflammation</a> at <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044678/" class="def">injection</a> sites.</div></li><li class="half_rhythm"><div>Headache.</div></li><li class="half_rhythm"><div>Fever.</div></li><li class="half_rhythm"><div>Chills.</div></li></ul><p id="CDR0000269596__205">One <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000691484/" class="def">meta-analysis</a> using <i>Viscum album</i> L. and isolated <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044994/" class="def">mistletoe lectins</a> included both <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000454774/" class="def">animal</a> and human studies. <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044664/" class="def">Doses</a> and application forms varied. No <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044041/" class="def">immunosuppressive</a> effects were reported. Side effects included local reactions at the injection site and flu-like symptoms such as <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000450108/" class="def">fever</a>, chills, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000321374/" class="def">fatigue</a>, mild <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045692/" class="def">gastrointestinal</a> symptoms, and headache. High doses of recombinantly-produced mistletoe lectins (not available in commercial products) resulted in reversible hepatotoxicity in some cases.[<a class="bibr" href="#CDR0000269596_rl_52_5" rid="CDR0000269596_rl_52_5">5</a>] Another review reported adverse reactions that included local reactions at the injection site, fever, increased intracerebral pressure, headache, circulatory problems, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046615/" class="def">thrombophlebitis</a>, swelling of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045762/" class="def">lymph nodes</a>, and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000443292/" class="def">allergic reactions</a>.[<a class="bibr" href="#CDR0000269596_rl_52_6" rid="CDR0000269596_rl_52_6">6</a>]</p><p id="CDR0000269596__206"> A few cases of severe allergic reactions, including <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285952/" class="def">anaphylactic shock</a>, have been reported.[<a class="bibr" href="#CDR0000269596_rl_52_2" rid="CDR0000269596_rl_52_2">2</a>]</p><p id="CDR0000269596__295">Although from an <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000286105/" class="def">observational</a> cohort study, three types of mistletoe (Iscador, Helixor, and abnobaVISCUM) that were given <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044603/" class="def">intratumorally</a>, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046682/" class="def">intravenously</a>, or <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045914/" class="def">subcutaneously</a> were found to be safe in a small group of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045333/" class="def">cancer</a> patients with autoimmune diseases such as Graves disease, Hashimoto <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000455472/" class="def">thyroiditis</a>, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045493/" class="def">ulcerative colitis</a>, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044219/" class="def">psoriasis</a>, and some rheumatic diseases.[<a class="bibr" href="#CDR0000269596_rl_52_7" rid="CDR0000269596_rl_52_7">7</a>]</p><div id="CDR0000269596_rl_52"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000269596_rl_52_1">Kaegi E: Unconventional therapies for cancer: 3. Iscador. Task Force on Alternative Therapies of the Canadian Breast Cancer Research Initiative. CMAJ 158 (9): 1157-9, 1998. [<a href="/pmc/articles/PMC1229273/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1229273</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/9597967" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9597967</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_52_2">Hutt N, Kopferschmitt-Kubler M, Cabalion J, et al.: Anaphylactic reactions after therapeutic injection of mistletoe (Viscum album L.). Allergol Immunopathol (Madr) 29 (5): 201-3, 2001 Sep-Oct. [<a href="https://pubmed.ncbi.nlm.nih.gov/11720654" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11720654</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_52_3">Stauder H, Kreuser ED: Mistletoe extracts standardised in terms of mistletoe lectins (ML I) in oncology: current state of clinical research. Onkologie 25 (4): 374-80, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/12232491" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12232491</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_52_4">Steele ML, Axtner J, Happe A, et al.: Safety of Intravenous Application of Mistletoe (Viscum album L.) Preparations in Oncology: An Observational Study. Evid Based Complement Alternat Med 2014: 236310, 2014. [<a href="/pmc/articles/PMC4052504/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4052504</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24955100" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24955100</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_52_5">Kienle GS, Grugel R, Kiene H: Safety of higher dosages of Viscum album L. in animals and humans--systematic review of immune changes and safety parameters. BMC Complement Altern Med 11: 72, 2011. [<a href="/pmc/articles/PMC3180269/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3180269</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21871125" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21871125</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_52_6">Ernst E, Schmidt K, Steuer-Vogt MK: Mistletoe for cancer? A systematic review of randomised clinical trials. Int J Cancer 107 (2): 262-7, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/12949804" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12949804</span></a>]</div></li><li><div class="bk_ref" id="CDR0000269596_rl_52_7">Oei SL, Thronicke A, Kröz M, et al.: Use and Safety of Viscum album L Applications in Cancer Patients With Preexisting Autoimmune Diseases: Findings From the Network Oncology Study. Integr Cancer Ther 18: 1534735419832367, 2019 Jan-Dec. [<a href="/pmc/articles/PMC6432670/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6432670</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30808274" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30808274</span></a>]</div></li></ol></div></div><div id="CDR0000269596__55"><h2 id="_CDR0000269596__55_">Summary of the Evidence for Mistletoe Extracts</h2><p id="CDR0000269596__474">To assist readers in evaluating the results of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044195/" class="def">human studies</a> of integrative, alternative, and complementary therapies for <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045333/" class="def">cancer</a>, the strength of the evidence (i.e., the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000446533/" class="def">levels of
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evidence</a>) associated with each type of treatment is provided whenever
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possible. To qualify for a level of evidence <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000390238/" class="def">analysis</a>, a study must:</p><ul id="CDR0000269596__475"><li class="half_rhythm"><div>Be published in a <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000537399/" class="def">peer-reviewed scientific journal</a>.</div></li><li class="half_rhythm"><div>Report on a <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000043985/" class="def">therapeutic</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000467853/" class="def">outcome</a> or outcomes, such as <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046634/" class="def">tumor</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044085/" class="def">response</a>, improvement in survival, or measured improvement in <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045417/" class="def">quality of life</a>.</div></li><li class="half_rhythm"><div>Describe <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044168/" class="def">clinical</a> findings in sufficient detail that a meaningful evaluation can be made.</div></li></ul><p id="CDR0000269596__476">Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044724/" class="def">scientific</a> strength of the treatment outcomes (i.e., <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000346519/" class="def">endpoints</a>) measured. The resulting two scores are then combined to produce an overall score. For an explanation of the scores and additional information about levels of evidence analysis for cancer, see <a href="/books/n/pdqcis/CDR0000256874/?report=reader">Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies</a>.</p><p id="CDR0000269596__56"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285939/" class="def">Mistletoe</a> is one of the most widely studied <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044964/" class="def">complementary and alternative medicine</a> therapies for cancer. In certain European countries, the preparations made from European mistletoe (<i>Viscum album</i> L.) are among the most prescribed drugs offered to cancer patients. Mistletoe <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000407760/" class="def">extracts</a> have been evaluated in numerous <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044195/" class="def">clinical studies</a> and improvements in survival, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045417/" class="def">quality of life</a>, and/or stimulation of the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046356/" class="def">immune system</a> have been frequently reported. However, most clinical studies conducted have had one or more major weaknesses that raise doubts about the reliability of the findings. In addition, no evidence exists to support the notion that stimulation of the immune system by mistletoe leads to an improved ability to fight cancer. Because all patients in the reported clinical studies appear to have been adults, no information is available about the use of mistletoe as a treatment for children with cancer. </p></div><div id="CDR0000269596__62"><h2 id="_CDR0000269596__62_">Latest Updates to This Summary (11/06/2024)</h2><p id="CDR0000269596__63">The <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044271/" class="def">PDQ</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045333/" class="def">cancer</a> information summaries are reviewed regularly and updated as
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new information becomes available. This section describes the latest
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changes made to this summary as of the date above.</p><p id="CDR0000269596__487">Editorial changes were made to this summary.</p><p id="CDR0000269596__disclaimerHP_3">This summary is written and maintained by the <a href="https://www.cancer.gov/publications/pdq/editorial-boards/cam" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Integrative, Alternative, and Complementary Therapies Editorial Board</a>, which is
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editorially independent of NCI. The summary reflects an independent review of
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the literature and does not represent a policy statement of NCI or NIH. More
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information about summary policies and the role of the PDQ Editorial Boards in
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maintaining the PDQ summaries can be found on the <a href="#CDR0000269596__AboutThis_1">About This PDQ Summary</a> and <a href="https://www.cancer.gov/publications/pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ® Cancer Information for Health Professionals</a> pages.
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</p></div><div id="CDR0000269596__AboutThis_1"><h2 id="_CDR0000269596__AboutThis_1_">About This PDQ Summary</h2><div id="CDR0000269596__AboutThis_2"><h3>Purpose of This Summary</h3><p id="CDR0000269596__AboutThis_3">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of mistletoe extracts in the treatment of people with cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.</p></div><div id="CDR0000269596__AboutThis_4"><h3>Reviewers and Updates</h3><p id="CDR0000269596__AboutThis_5">This summary is reviewed regularly and updated as necessary by the <a href="https://www.cancer.gov/publications/pdq/editorial-boards/cam" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Integrative, Alternative, and Complementary Therapies Editorial Board</a>, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p><p id="CDR0000269596__AboutThis_22"> Board members review recently published articles each month to determine whether an article should:</p><ul id="CDR0000269596__AboutThis_6"><li class="half_rhythm"><div>be discussed at a meeting,</div></li><li class="half_rhythm"><div>be cited with text, or</div></li><li class="half_rhythm"><div>replace or update an existing article that is already cited.</div></li></ul><p id="CDR0000269596__AboutThis_7">Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.</p><p id="CDR0000269596__AboutThis_9">Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.</p></div><div id="CDR0000269596__AboutThis_10"><h3>Levels of Evidence</h3><p id="CDR0000269596__AboutThis_11">Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Integrative, Alternative, and Complementary Therapies Editorial Board uses a <a href="/books/n/pdqcis/CDR0000256874/?report=reader">formal evidence ranking system</a> in developing its level-of-evidence designations.</p></div><div id="CDR0000269596__AboutThis_12"><h3>Permission to Use This Summary</h3><p id="CDR0000269596__AboutThis_13">PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”</p><p id="CDR0000269596__AboutThis_14">The preferred citation for this PDQ summary is:</p><p id="CDR0000269596__AboutThis_15">PDQ® Integrative, Alternative, and Complementary Therapies Editorial Board. PDQ Mistletoe Extracts. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: <a href="https://www.cancer.gov/about-cancer/treatment/cam/hp/mistletoe-pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://www.cancer.gov/about-cancer/treatment/cam/hp/mistletoe-pdq</a>. Accessed <MM/DD/YYYY>. [PMID: 26389489]</p><p id="CDR0000269596__AboutThis_16">Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in <a href="https://visualsonline.cancer.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Visuals Online</a>, a collection of over 2,000 scientific images.
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</p></div><div id="CDR0000269596__AboutThis_17"><h3>Disclaimer</h3><p id="CDR0000269596__AboutThis_19">The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the <a href="https://www.cancer.gov/about-cancer/managing-care" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Managing Cancer Care</a> page.</p></div><div id="CDR0000269596__AboutThis_20"><h3>Contact Us</h3><p id="CDR0000269596__AboutThis_21">More information about contacting us or receiving help with the Cancer.gov website can be found on our <a href="https://www.cancer.gov/contact" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Contact Us for Help</a> page. Questions can also be submitted to Cancer.gov through the website’s <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>.</p></div></div></div></div><div class="fm-sec"><h2 id="_NBK66054_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><p class="contrib-group"><h4>Authors</h4><span itemprop="author">PDQ Integrative, Alternative, and Complementary Therapies Editorial Board</span>.</p><h3>Publication History</h3><p class="small">Published online: November 6, 2024.</p><p class="small">Created: <span itemprop="datePublished">December 21, 2002</span>.</p><h3>Version History</h3><ul class="simple-list" style="padding:0"><li><span class="bk_col_itm">NBK66054.25</span> November 6, 2024 (Displayed Version)</li><li><span class="bk_col_itm"><a href="/books/NBK66054.24/?report=reader">NBK66054.24</a></span> June 13, 2024</li><li><span class="bk_col_itm"><a href="/books/NBK66054.23/?report=reader">NBK66054.23</a></span> June 8, 2023</li><li><span class="bk_col_itm"><a href="/books/NBK66054.22/?report=reader">NBK66054.22</a></span> January 13, 2023</li><li><span class="bk_col_itm"><a href="/books/NBK66054.21/?report=reader">NBK66054.21</a></span> May 17, 2022</li><li><span class="bk_col_itm"><a href="/books/NBK66054.20/?report=reader">NBK66054.20</a></span> April 14, 2022</li><li><span class="bk_col_itm"><a href="/books/NBK66054.19/?report=reader">NBK66054.19</a></span> October 27, 2021</li><li><span class="bk_col_itm"><a href="/books/NBK66054.18/?report=reader">NBK66054.18</a></span> March 17, 2021</li><li><span class="bk_col_itm"><a href="/books/NBK66054.17/?report=reader">NBK66054.17</a></span> August 11, 2020</li><li><span class="bk_col_itm"><a href="/books/NBK66054.16/?report=reader">NBK66054.16</a></span> June 4, 2020</li><li><span class="bk_col_itm"><a href="/books/NBK66054.15/?report=reader">NBK66054.15</a></span> April 22, 2020</li><li><span class="bk_col_itm"><a href="/books/NBK66054.14/?report=reader">NBK66054.14</a></span> October 25, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK66054.13/?report=reader">NBK66054.13</a></span> April 9, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK66054.12/?report=reader">NBK66054.12</a></span> October 5, 2018</li><li><span class="bk_col_itm"><a href="/books/NBK66054.11/?report=reader">NBK66054.11</a></span> September 6, 2018</li><li><span class="bk_col_itm"><a href="/books/NBK66054.10/?report=reader">NBK66054.10</a></span> August 15, 2018</li><li><span class="bk_col_itm"><a href="/books/NBK66054.9/?report=reader">NBK66054.9</a></span> November 6, 2017</li><li><span class="bk_col_itm"><a href="/books/NBK66054.8/?report=reader">NBK66054.8</a></span> February 15, 2017</li><li><span class="bk_col_itm"><a href="/books/NBK66054.7/?report=reader">NBK66054.7</a></span> October 19, 2016</li><li><span class="bk_col_itm"><a href="/books/NBK66054.6/?report=reader">NBK66054.6</a></span> September 7, 2016</li><li><span class="bk_col_itm"><a href="/books/NBK66054.5/?report=reader">NBK66054.5</a></span> April 15, 2016</li><li><span class="bk_col_itm"><a href="/books/NBK66054.4/?report=reader">NBK66054.4</a></span> April 1, 2016</li><li><span class="bk_col_itm"><a href="/books/NBK66054.3/?report=reader">NBK66054.3</a></span> January 22, 2016</li><li><span class="bk_col_itm"><a href="/books/NBK66054.2/?report=reader">NBK66054.2</a></span> September 30, 2015</li><li><span class="bk_col_itm"><a href="/books/NBK66054.1/?report=reader">NBK66054.1</a></span> March 24, 2015</li></ul><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><a href="http://www.cancer.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Cancer Institute (US)</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>PDQ Integrative, Alternative, and Complementary Therapies Editorial Board. Mistletoe Extracts (PDQ®): Health Professional Version. 2024 Nov 6. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"></div><div class="small-screen-next"></div></article><article data-type="table-wrap" id="figobCDR0000269596257"><div id="CDR0000269596__257" class="table"><h3><span class="title">Table 1. <i>In Vitro</i> Studies<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK66054/table/CDR0000269596__257/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000269596__257_lrgtbl__"><table class="no_margin"><tbody><tr><td colspan="3" rowspan="1" style="text-align:left;vertical-align:top;">
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<b>Iscador</b>
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</td></tr><tr><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
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<b>Cell Line</b>
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</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
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<b>Outcome</b>
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</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
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<b>Reference</b>
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</td></tr><tr><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">Various human cancer cell
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lines</td><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">Iscador preparations containing a high lectin concentration (15 μg/<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044214/" class="def">mL</a>) showed >70% growth inhibition in the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044560/" class="def">mammary</a> cancer cell line (MAXF 401NL) compared with untreated control cells; 30%–70% growth inhibition in three <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046634/" class="def">tumor</a> cell lines (<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045343/" class="def">leukemia</a> RPMI 8226, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045323/" class="def">non-small cell lung</a> LXFE 66NL, and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000445094/" class="def">uterine</a> UXF 1138L) for IscadorM and in seven tumor cell lines (<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046481/" class="def">central nervous system</a> SF268, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000454513/" class="def">gastric</a> GXF 251L, non-small cell lung LXFE 66NL and LXFL 529L, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000445079/" class="def">prostate</a> PC3M, renal RXF 944L, and uterine UXF 1138L) for IscadorQu</td><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_35" rid="CDR0000269596_rl_23_35">35</a>]
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</td></tr><tr><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">Human
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045780/" class="def">medulloblastoma</a> cells
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Daoy, D341, D425, and UW 228-2 </td><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;"><i>Viscum album</i> preparations (0.1–100 <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000306521/" class="def">µg</a>/mL) induced cell death through <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046524/" class="def">apoptosis</a>. Growth-inhibition correlated with the lectin content of the used preparation</td><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_37" rid="CDR0000269596_rl_23_37">37</a>]
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</td></tr><tr><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">Various human cancer cell lines: SF268 (central nervous system); GXF 251 (gastric); H460, LXFA 629L, LXFE 66NL, LXFL 529L (lung); CCRFCEM, MOLT-4, HL-60, K562, U937, RPMI 8226 (leukemia and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045368/" class="def">lymphoma</a>); MCF7, MAXF 401NL (mammary); HT144, MALME-3M, SK-MEL28, MEXF 462NL, MEXF 514L (<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045135/" class="def">melanoma</a>); PC3M (prostate); RXF 393NL, RXF 944L (renal); Hs729, SK-LMS-1, SK-UT-1B (<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045562/" class="def">sarcoma</a>); and UXF 1138L (uterus)</td><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">IscadorM and IscadorQu with a high lectin content demonstrated <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000446109/" class="def">antitumor</a> activity <i>in vitro</i> at high test concentrations (15–150 µg/mL)</td><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_38" rid="CDR0000269596_rl_23_38">38</a>]
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</td></tr><tr><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">Human cell lines: HCC1937, HCC1143 (breast), PA-TU-8902 (<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046254/" class="def">pancreas</a>), DU145 (prostate), NCI-H460 (lung)</td><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">Cell proliferation inhibition was detected with a mistletoe dose at 100 μg/mL in cell lines PA-TU-8902 and NCI-H460, and a dose at ≥10 μg/mL in cell lines HCC1937, HCC1143, and DU145</td><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_40" rid="CDR0000269596_rl_23_40">40</a>]
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</td></tr><tr><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045698/" class="def">Glioblastoma</a> cells: LNT-229, LN-308</td><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">Cell growth was reduced with IscadorQ and IscadorM at lectin concentrations of 100 µg/mL</td><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_41" rid="CDR0000269596_rl_23_41">41</a>]
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</td></tr><tr><td colspan="3" rowspan="1" style="text-align:left;vertical-align:top;">
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<b>Helixor</b>
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</td></tr><tr><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;"><b>Cell Line</b>
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</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
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<b>Outcome</b>
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</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
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<b>Reference</b>
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</td></tr><tr><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">Various human cancer cell lines</td><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">Helixor mistletoe preparations (15–150 µg/mL) and ML-1 (10–100 ng/mL) did not induce cell proliferation</td><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_39" rid="CDR0000269596_rl_23_39">39</a>]
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</td></tr><tr><td colspan="3" rowspan="1" style="text-align:left;vertical-align:top;">
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<b>abnobaVISCUM</b>
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</td></tr><tr><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
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<b>Cell Line</b>
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</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
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<b>Outcome</b>
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</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
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<b>Reference</b>
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</td></tr><tr><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">Human tumor cell lines: <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045611/" class="def">B-cell</a> hybridomas, P815, EL-4, Ke37, MOLT-4, and U937</td><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">Growth arrest was caused by the induction of apoptosis (50% of U937 cells at 100 ng/mL of ML-1 and 40% of B-cell hybridomas and EL-4 cells at concentrations as low as 1 ng/mL of ML-1)</td><td colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_10" rid="CDR0000269596_rl_23_10">10</a>]
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">IscadorQu = IscadorQ; ML-1 = mistletoe extracts with mistletoe lectins I.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><sup>a</sup>For more information and definition of terms, see text and the <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI Dictionary of Cancer Terms</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobCDR0000269596258"><div id="CDR0000269596__258" class="table"><h3><span class="title">Table 2. <i><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046352/" class="def">In Vivo</a></i> Studies<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK66054/table/CDR0000269596__258/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000269596__258_lrgtbl__"><table class="no_margin"><tbody><tr><td colspan="3" rowspan="1" style="vertical-align:top;">
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<b>Iscador</b>
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</td></tr><tr><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
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<b>Animal Model</b>
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</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
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<b>Outcome</b>
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</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
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<b>Reference</b>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Mice</td><td colspan="1" rowspan="1" style="vertical-align:top;">Antiproliferative and antimetastatic effects in melanoma cell line MV3 were only achieved with low-dose ML-1 (30 ng/kg body weight) and not with higher doses (150 ng/kg and 500 ng/kg); increased number of infiltrating <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044948/" class="def">dendritic cells</a> suggests stimulation of the immune system</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_44" rid="CDR0000269596_rl_23_44">44</a>]
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Mice</td><td colspan="1" rowspan="1" style="vertical-align:top;"><i>Viscum album</i> extract (20 µg/mouse/d) mediated inhibition of B16F1 melanoma cells tumor growth was associated with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000367426/" class="def">immunomodulation</a> via induction of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044418/" class="def">IL-12</a> secretion leading to enhanced <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044928/" class="def">T-cell</a> and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044439/" class="def">NK-cell</a> functions</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_45" rid="CDR0000269596_rl_23_45">45</a>]
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Mice</td><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000257523/" class="def">Organ</a> colonization was investigated on day 14 after RAW 117 H 10 <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044115/" class="def">lymphosarcoma</a> cell and L-1 sarcoma cell inoculation and demonstrated <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044167/" class="def">statistically significant</a> (<i>P</i> < .05) reductions of <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044758/" class="def">experimental</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046312/" class="def">liver</a> and lung <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046710/" class="def">metastases</a> for standardized <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000043998/" class="def">aqueous</a> mistletoe extract–treated mice (2 µg, 20 µg, 100 µg, and 500 µg per mouse)</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_47" rid="CDR0000269596_rl_23_47">47</a>]
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Mice (Nude and VMDk mice)</td><td colspan="1" rowspan="1" style="vertical-align:top;">Glioblastoma tumor growth was reduced (cell lines LNT-229 and LN-308), the expression of <a href="/books/n/pdqcis/glossary_gen/def-item/glossary_gen_CDR0000045693/" class="def">genes</a> associated with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045669/" class="def">tumor progression</a> was reduced, and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044439/" class="def">NK cell</a> mediated glioblastoma cell <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044606/" class="def">lysis</a> was enhanced when IscadorQ and IscadorM 100 µg/mL was administered by an <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044603/" class="def">intratumoral</a> injection</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_41" rid="CDR0000269596_rl_23_41">41</a>]
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">BDF and Swiss albino mice</td><td colspan="1" rowspan="1" style="vertical-align:top;">Treatment with IscadorM (50 <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044213/" class="def">mg</a>/kg/d and 100 mg/kg/d) increased the survival time of mice that had been implanted with Ehrlich ascites mouse cancer cells, but not L1210 leukemia or B16 melanoma cancer cells</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_51" rid="CDR0000269596_rl_23_51">51</a>]
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Swiss albino mice</td><td colspan="1" rowspan="1" style="vertical-align:top;">No antitumor effect or improvement in survival was observed when IscadorM (15.75 mg, 750 mg, 10.5 mg, 500 mg) was used to treat rats bearing chemically induced mammary <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045963/" class="def">carcinomas</a> or tumors formed from rat Walker 256 carcinosarcoma cells; IscadorM (5 mg, 200 mg, 150 mg, 3.75 mg) was also not effective in treating mice that had been injected with Ehrlich ascites cells; in addition, IscadorP (135 mg) was found ineffective in treating rats with tumors formed from rat L5222 leukemia cells</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_52" rid="CDR0000269596_rl_23_52">52</a>]
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</td></tr><tr><td colspan="3" rowspan="1" style="text-align:left;vertical-align:top;">
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<b>Helixor</b>
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</td></tr><tr><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
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<b>Animal Model</b>
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</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
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<b>Outcome</b>
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</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
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<b>Reference</b>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000615419/" class="def">SCID</a> mice</td><td colspan="1" rowspan="1" style="vertical-align:top;">Despite a considerably lower ML-3 content, MT-A (50 mg/kg and 100 mg/kg) was more effective and less <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000043986/" class="def">toxic</a> than MT-P (50 mg/kg) in a human <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045586/" class="def">acute lymphoblastic leukemia</a> cell line (NALM-6); both were given intraperitoneally in mice inoculated with human ALL</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_43" rid="CDR0000269596_rl_23_43">43</a>]
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Human <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046441/" class="def">ductal</a> breast carcinoma cell line BT474</td><td colspan="1" rowspan="1" style="vertical-align:top;">As compared with tumors of control mice, tumors of the ME-A– and ME-M–treated groups (5 mg intratumoral injection) showed a decreased cell proliferation rate, as well as an increased cell <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044290/" class="def">necrosis</a> and apoptosis rate</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_46" rid="CDR0000269596_rl_23_46">46</a>]
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</td></tr><tr><td colspan="3" rowspan="1" style="vertical-align:top;">
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<b>abnobaVISCUM</b>
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</td></tr><tr><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
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<b>Animal Model</b>
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</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
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<b>Outcome</b>
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</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
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<b>Reference</b>
|
|
</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Nude mice</td><td colspan="1" rowspan="1" style="vertical-align:top;">Intratumoral injections of mistletoe extract (abnobaVISCUM Fraxini-2, 8 mg/kg body weight and lectin at 5.3 µg/kg body weight) demonstrated more antitumor activity than did <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046682/" class="def">intravenous</a>
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<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000508951/" class="def">gemcitabine</a> when injected into mice bearing xenografts of human <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044521/" class="def">pancreatic adenocarcinoma cancer</a> (PAXF 736)</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_53" rid="CDR0000269596_rl_23_53">53</a>]
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</td></tr><tr><td colspan="3" rowspan="1" style="vertical-align:top;">
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<b>Isorel</b>
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</td></tr><tr><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
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<b>Animal Model</b>
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</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
|
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<b>Outcome</b>
|
|
</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
|
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<b>Reference</b>
|
|
</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Mice</td><td colspan="1" rowspan="1" style="vertical-align:top;">In mice <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046631/" class="def">transplanted</a> with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046403/" class="def">fibrosarcoma</a> (CMC-2), when IsorelM (140 mg/kg) was used alone, no effect on either tumor growth or animal survival was observed. When IsorelM (140 mg/kg) was combined with <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044302/" class="def">x-ray therapy</a> of tumors, there was substantial improvements in survival of mice compared with survival of mice treated with x-ray therapy (43 Gy) alone</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_54" rid="CDR0000269596_rl_23_54">54</a>]
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</td></tr><tr><td colspan="3" rowspan="1" style="vertical-align:top;">
|
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<b>Eurixor</b>
|
|
</td></tr><tr><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
|
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<b>Animal Model</b>
|
|
</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
|
|
<b>Outcome</b>
|
|
</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
|
|
<b>Reference</b>
|
|
</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Mice</td><td colspan="1" rowspan="1" style="vertical-align:top;">Aqueous mistletoe extract (30 ng/mL or 300 ng/mL) showed antitumoral activity on <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044093/" class="def">urinary</a>
|
|
<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046501/" class="def">bladder</a> carcinoma (MB49) in mice, which was considered to be mainly caused by the cytotoxic properties of mistletoe lectins</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_6" rid="CDR0000269596_rl_23_6">6</a>]
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</td></tr><tr><td colspan="3" rowspan="1" style="vertical-align:top;">
|
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<b>Lektinol</b>
|
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</td></tr><tr><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
|
|
<b>Animal Model</b>
|
|
</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
|
|
<b>Outcome</b>
|
|
</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">
|
|
<b>Reference</b>
|
|
</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Mice</td><td colspan="1" rowspan="1" style="vertical-align:top;">Treatment with Lektinol (0.3, 3, 30, or 300 ng/mL/kg/d) slowed the growth of tumors formed in mice from implants of three types of mouse cancers (<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046462/" class="def">colon</a> adenocarcinoma 38, Renca <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000661352/" class="def">renal cell carcinoma</a>, and F9 <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046611/" class="def">testicular</a> carcinoma) but not from two other mouse cancers (B16 melanoma and Lewis lung carcinoma)</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_23_7" rid="CDR0000269596_rl_23_7">7</a>]
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ALL = acute lymphoblastic leukemia; ME-A = mistletoe extracts (fir tree <i>Abies</i>); ME-M = mistletoe extracts (apple tree <i>Malus</i>); ML-1 = mistletoe extracts with mistletoe lectins I; ML-3 = mistletoe extracts with mistletoe lectins III; MT-A = mistletoe extracts obtained from fir trees; MT-P = mistletoe extracts obtained from pine trees; NK = natural killer.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><sup>a</sup>For more information and definition of terms, see text and the <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI Dictionary of Cancer Terms</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobCDR0000269596194"><div id="CDR0000269596__194" class="table"><h3><span class="title">Table 3. Use of Iscador in Cancer Treatment: Clinical Reports Describing Therapeutic End Points<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK66054/table/CDR0000269596__194/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000269596__194_lrgtbl__"><table class="no_margin"><thead><tr><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Reference </th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Trial Design </th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000651193/" class="def">Condition</a> or Cancer Type </th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Treatment Groups (Enrolled; Treated; Placebo or No Treatment Control)<sup>b</sup>
|
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</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Results</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044011/" class="def">Concurrent Therapy</a> Used<sup>c</sup></th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000446533/" class="def">Level of Evidence</a> Score<sup>d</sup></th></tr></thead><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
|
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[<a class="bibr" href="#CDR0000269596_rl_35_26" rid="CDR0000269596_rl_35_26">26</a>]
|
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Randomized trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">Lung, non-small cell, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285970/" class="def">inoperable</a></td><td colspan="1" rowspan="1" style="vertical-align:top;">408; 105; 107<sup>e</sup></td><td colspan="1" rowspan="1" style="vertical-align:top;">Subjective improvement in QOL</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes<sup>f</sup></td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">1iiA</a>
|
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
|
|
[<a class="bibr" href="#CDR0000269596_rl_35_35" rid="CDR0000269596_rl_35_35">35</a>]
|
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Randomized trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">Lung, non-small cell, stages I–IV </td><td colspan="1" rowspan="1" style="vertical-align:top;">218; 87; 96</td><td colspan="1" rowspan="1" style="vertical-align:top;">Improved median survival, LN+ patients only</td><td colspan="1" rowspan="1" style="vertical-align:top;">No</td><td colspan="1" rowspan="1" style="vertical-align:top;">
|
|
<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">1iiA</a>
|
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
|
|
[<a class="bibr" href="#CDR0000269596_rl_35_5" rid="CDR0000269596_rl_35_5">5</a>]
|
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Randomized trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">Melanoma, stages II–III</td><td colspan="1" rowspan="1" style="vertical-align:top;">204; 102; 102</td><td colspan="1" rowspan="1" style="vertical-align:top;">No improvement in DFS or OS rates</td><td colspan="1" rowspan="1" style="vertical-align:top;">No</td><td colspan="1" rowspan="1" style="vertical-align:top;">
|
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">1iiA</a>
|
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
|
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[<a class="bibr" href="#CDR0000269596_rl_35_37" rid="CDR0000269596_rl_35_37">37</a>
|
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,<a class="bibr" href="#CDR0000269596_rl_35_40" rid="CDR0000269596_rl_35_40">40</a>]
|
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Randomized trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">Pancreatic, advanced or metastatic</td><td colspan="1" rowspan="1" style="vertical-align:top;">220; 110; 110</td><td colspan="1" rowspan="1" style="vertical-align:top;">Improved OS </td><td colspan="1" rowspan="1" style="vertical-align:top;">No</td><td colspan="1" rowspan="1" style="vertical-align:top;">
|
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">1iiA</a>
|
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
|
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[<a class="bibr" href="#CDR0000269596_rl_35_27" rid="CDR0000269596_rl_35_27">27</a>]
|
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Randomized trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">Osteosarcoma, second metastatic relapse</td><td colspan="1" rowspan="1" style="vertical-align:top;">20; 9 (viscum); 11 (etoposide)</td><td colspan="1" rowspan="1" style="vertical-align:top;">Improved DFS compared with etoposide group</td><td colspan="1" rowspan="1" style="vertical-align:top;">No</td><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335129/" class="def">1iiDii</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
|
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[<a class="bibr" href="#CDR0000269596_rl_35_41" rid="CDR0000269596_rl_35_41">41</a>]
|
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Randomized trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">Breast</td><td colspan="1" rowspan="1" style="vertical-align:top;">95; 30 (IscadorM) and 34 (HelixorA); 31</td><td colspan="1" rowspan="1" style="vertical-align:top;">No differences in the primary outcome between groups</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">
|
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335127/" class="def">1iiC</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
|
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[<a class="bibr" href="#CDR0000269596_rl_35_29" rid="CDR0000269596_rl_35_29">29</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Comparative, retrolective, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000285673/" class="def">cohort study</a>
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Breast, stages I–IV</td><td colspan="1" rowspan="1" style="vertical-align:top;">1,442; 710; 732</td><td colspan="1" rowspan="1" style="vertical-align:top;">Fewer adverse drug reactions with mistletoe</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">
|
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335133/" class="def">2B</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_28" rid="CDR0000269596_rl_35_28">28</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Comparative, retrolective, cohort study </td><td colspan="1" rowspan="1" style="vertical-align:top;">Melanoma, stages II–III</td><td colspan="1" rowspan="1" style="vertical-align:top;">686; 329; 357</td><td colspan="1" rowspan="1" style="vertical-align:top;">Improved overall disease-specific survival</td><td colspan="1" rowspan="1" style="vertical-align:top;">Unknown</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335132/" class="def">2A</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_4" rid="CDR0000269596_rl_35_4">4</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Cohort study</td><td colspan="1" rowspan="1" style="vertical-align:top;">Breast, stage III</td><td colspan="1" rowspan="1" style="vertical-align:top;">8,475<sup>g</sup>; 17<sup>h</sup>; 17<sup>h</sup>
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Improved mean survival</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">None</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_4" rid="CDR0000269596_rl_35_4">4</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Cohort study </td><td colspan="1" rowspan="1" style="vertical-align:top;">Various types, stages I–IV</td><td colspan="1" rowspan="1" style="vertical-align:top;">8,475<sup>g</sup>; 39<sup>h</sup>; 39<sup>h</sup></td><td colspan="1" rowspan="1" style="vertical-align:top;">Improved mean survival</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">None</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_4" rid="CDR0000269596_rl_35_4">4</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Cohort study </td><td colspan="1" rowspan="1" style="vertical-align:top;">Various types, stages I–IV</td><td colspan="1" rowspan="1" style="vertical-align:top;">10,226<sup>g</sup>; 396<sup>h</sup>; 396<sup>h</sup></td><td colspan="1" rowspan="1" style="vertical-align:top;">Improved mean survival</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">None</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_33" rid="CDR0000269596_rl_35_33">33</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Retrospective, observational, cohort study </td><td colspan="1" rowspan="1" style="vertical-align:top;">Nonmetastatic colorectal</td><td colspan="1" rowspan="1" style="vertical-align:top;">804; 429; 375</td><td colspan="1" rowspan="1" style="vertical-align:top;">Lower <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000046145/" class="def">incidence</a> of diarrhea, nausea, loss of appetite, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045667/" class="def">dermatitis</a>, fatigue, and mucositis</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">
|
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335134/" class="def">2C</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
|
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[<a class="bibr" href="#CDR0000269596_rl_35_38" rid="CDR0000269596_rl_35_38">38</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Retrospective analysis study</td><td colspan="1" rowspan="1" style="vertical-align:top;">Pancreatic</td><td colspan="1" rowspan="1" style="vertical-align:top;">206 (subgroup of 142 using survival data on 124); 25 (chemotherapy alone); 48 (chemotherapy and mistletoe), 50 (chemotherapy, mistletoe, and hyperthermia); 1 (chemotherapy and hyperthermia)</td><td colspan="1" rowspan="1" style="vertical-align:top;"> Improved survival was reported in the triplet arm</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335132/" class="def">2A</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_39" rid="CDR0000269596_rl_35_39">39</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044575/" class="def">Nonconsecutive case series</a>
|
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Pancreatic </td><td colspan="1" rowspan="1" style="vertical-align:top;">292; 292; various historical controls</td><td colspan="1" rowspan="1" style="vertical-align:top;">Improved median survival</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">
|
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335150/" class="def">3iiiA</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">DFS = disease-free survival; LN+ = lymph node–positive disease; No. = number; OS = overall survival; QOL = quality of life.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><sup>a</sup>For more information and definition of terms, see text and the <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI Dictionary of Cancer Terms</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><sup>b</sup>Number of patients treated plus number of patients controlled may not equal number of patients enrolled; number of patients enrolled = number of patients initially recruited/considered by the researchers who conducted a study; number of patients treated = number of enrolled patients who were administered the treatment being studied and for whom results were reported; <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044596/" class="def">historical control subjects</a> are not included in number of patients enrolled.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><sup>c</sup>Chemotherapy, radiation therapy, hormonal therapy, or <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000797582/" class="def">cytokine therapy</a> administered/allowed at the same time as mistletoe therapy.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><sup>d</sup>For information about levels of evidence analysis and scores, see <a href="/books/n/pdqcis/CDR0000256874/?report=reader">Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><sup>e</sup>Control patients were treated with a vitamin B mixture as a placebo; 100 additional evaluable patients were treated with Polyerga Neu, a sheep spleen glycopeptide reported to be an immunostimulant and an inhibitor of tumor cell glycolysis; treatment with Polyerga Neu was not found to be beneficial.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><sup>f</sup>Radiation therapy for metastases distant from the site of the <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000045847/" class="def">primary tumor</a> was permitted; radiation therapy to the primary tumor site or use of other anticancer treatment was not permitted.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><sup>g</sup>Among 10,226 cancer patients enrolled in a retrospective matched-pair, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000348989/" class="def">case-control study</a>, 1,751 had been treated with Iscador or another mistletoe product and 8,475 had not been treated with mistletoe; from the 8,475 untreated patients, two sets of matched pairs were formed for prospective studies; in the prospective studies, one member of each pair was randomly assigned to be treated with Iscador and the other member served as a control subject.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><sup>h</sup>Patients were strictly matched according to sex, year of birth ± 3 years, year of diagnosis ± 3 years, type of tumor, stage of disease, and conventional therapy received.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobCDR000026959671"><div id="CDR0000269596__71" class="table"><h3><span class="title">Table 4. Use of Other Mistletoe Products in Cancer Treatment: Clinical Reports Describing Therapeutic End Points<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK66054/table/CDR0000269596__71/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000269596__71_lrgtbl__"><table class="no_margin"><thead><tr><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Reference </th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Trial Design</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Product Tested</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Condition or Cancer Type</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Treatment Groups (Enrolled; Treated; Placebo or No Treatment Control)<sup>b</sup></th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Results</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Concurrent Therapy Used<sup>c</sup></th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Level of Evidence Score<sup>d</sup></th></tr></thead><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_3" rid="CDR0000269596_rl_35_3">3</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Randomized trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">Eurixor</td><td colspan="1" rowspan="1" style="vertical-align:top;">Bladder, noninvasive</td><td colspan="1" rowspan="1" style="vertical-align:top;">45; 23; 22</td><td colspan="1" rowspan="1" style="vertical-align:top;">DFS did not vary between groups</td><td colspan="1" rowspan="1" style="vertical-align:top;">No</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335128/" class="def">1iiDi</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_1" rid="CDR0000269596_rl_35_1">1</a>
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,<a class="bibr" href="#CDR0000269596_rl_35_63" rid="CDR0000269596_rl_35_63">63</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Randomized trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">Eurixor</td><td colspan="1" rowspan="1" style="vertical-align:top;">Brain, glioma; 74% of patients, stages III–IV; 26% of
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patients,
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no stage
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information
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">47; 20; 18</td><td colspan="1" rowspan="1" style="vertical-align:top;">Improved survival,
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stages
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III–IV
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patients
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only
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">1iiA</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_52" rid="CDR0000269596_rl_35_52">52</a>
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,<a class="bibr" href="#CDR0000269596_rl_35_53" rid="CDR0000269596_rl_35_53">53</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Randomized trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">Eurixor</td><td colspan="1" rowspan="1" style="vertical-align:top;">Colorectal, metastatic</td><td colspan="1" rowspan="1" style="vertical-align:top;">107; 38; 41</td><td colspan="1" rowspan="1" style="vertical-align:top;">Improved QOL</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335127/" class="def">1iiC</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_2" rid="CDR0000269596_rl_35_2">2</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Randomized trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">Eurixor</td><td colspan="1" rowspan="1" style="vertical-align:top;">Head and neck,
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squamous
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cell,
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stages
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I–IV
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">495; 235<sup>e</sup>; 242<sup>e</sup></td><td colspan="1" rowspan="1" style="vertical-align:top;">No differences in DFS between groups</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes<sup>e</sup></td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335128/" class="def">1iiDi</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_45" rid="CDR0000269596_rl_35_45">45</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Randomized trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">Helixor</td><td colspan="1" rowspan="1" style="vertical-align:top;">Breast, stages I–III</td><td colspan="1" rowspan="1" style="vertical-align:top;">692; 192 (Helixor) and 177 (chemotherapy); 274</td><td colspan="1" rowspan="1" style="vertical-align:top;">Improved survival</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">1iiA</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_46" rid="CDR0000269596_rl_35_46">46</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Randomized trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">Helixor</td><td colspan="1" rowspan="1" style="vertical-align:top;">Colorectal, metastatic</td><td colspan="1" rowspan="1" style="vertical-align:top;">60; 20; 20</td><td colspan="1" rowspan="1" style="vertical-align:top;">Improved mean survival</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">1iiA</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_43" rid="CDR0000269596_rl_35_43">43</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Randomized trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">Helixor</td><td colspan="1" rowspan="1" style="vertical-align:top;">Breast, ovarian, and non-small cell lung </td><td colspan="1" rowspan="1" style="vertical-align:top;">224; 115; 109</td><td colspan="1" rowspan="1" style="vertical-align:top;">Improved QOL</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335127/" class="def">1iiC</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_41" rid="CDR0000269596_rl_35_41">41</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Randomized trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">HelixorA, IscadorM</td><td colspan="1" rowspan="1" style="vertical-align:top;">Breast</td><td colspan="1" rowspan="1" style="vertical-align:top;">95; 34 (HelixorA) and 30 (IscadorM); 31</td><td colspan="1" rowspan="1" style="vertical-align:top;">No differences in the primary outcome between groups</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335127/" class="def">1iiC</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_13" rid="CDR0000269596_rl_35_13">13</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Randomized controlled trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">PS76A (Lektin)</td><td colspan="1" rowspan="1" style="vertical-align:top;">Breast</td><td colspan="1" rowspan="1" style="vertical-align:top;">352; 176; 176</td><td colspan="1" rowspan="1" style="vertical-align:top;">Improved QOL</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335121/" class="def">1iC</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_57" rid="CDR0000269596_rl_35_57">57</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Randomized trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">Lektinol</td><td colspan="1" rowspan="1" style="vertical-align:top;">Breast</td><td colspan="1" rowspan="1" style="vertical-align:top;">261; 195; 66</td><td colspan="1" rowspan="1" style="vertical-align:top;">Improved QOL</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335121/" class="def">1iC</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_58" rid="CDR0000269596_rl_35_58">58</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Randomized trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">Lektinol</td><td colspan="1" rowspan="1" style="vertical-align:top;">Breast</td><td colspan="1" rowspan="1" style="vertical-align:top;">352; 176; 176</td><td colspan="1" rowspan="1" style="vertical-align:top;">Improved QOL</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335121/" class="def">1iC</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_56" rid="CDR0000269596_rl_35_56">56</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Randomized trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">Isorel</td><td colspan="1" rowspan="1" style="vertical-align:top;">Colorectal</td><td colspan="1" rowspan="1" style="vertical-align:top;">64; 50; 14 </td><td colspan="1" rowspan="1" style="vertical-align:top;">Improved survival and tolerance to either adjuvant or palliative treatment</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">1iiA</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_55" rid="CDR0000269596_rl_35_55">55</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Nonrandomized controlled trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">Isorel</td><td colspan="1" rowspan="1" style="vertical-align:top;">Digestive tract</td><td colspan="1" rowspan="1" style="vertical-align:top;">70; 40; 30</td><td colspan="1" rowspan="1" style="vertical-align:top;">Enhanced cellular immunity and improved QOL</td><td colspan="1" rowspan="1" style="vertical-align:top;">No</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335134/" class="def">2C</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_50" rid="CDR0000269596_rl_35_50">50</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Nonrandomized controlled trial</td><td colspan="1" rowspan="1" style="vertical-align:top;">abnobaVISCUM <i>Quercus</i></td><td colspan="1" rowspan="1" style="vertical-align:top;">Metastatic colorectal</td><td colspan="1" rowspan="1" style="vertical-align:top;">25; 25; none</td><td colspan="1" rowspan="1" style="vertical-align:top;">No objective tumor response</td><td colspan="1" rowspan="1" style="vertical-align:top;">Yes</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335137/" class="def">2Diii</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000269596_rl_35_21" rid="CDR0000269596_rl_35_21">21</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Nonrandomized controlled trial</td><td colspan="1" rowspan="1" style="vertical-align:top;"><i>Viscum fraxini</i>-2</td><td colspan="1" rowspan="1" style="vertical-align:top;">Hepatocellular carcinoma</td><td colspan="1" rowspan="1" style="vertical-align:top;">23; 23; none</td><td colspan="1" rowspan="1" style="vertical-align:top;">Improved survival </td><td colspan="1" rowspan="1" style="vertical-align:top;">No</td><td colspan="1" rowspan="1" style="vertical-align:top;">
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<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335136/" class="def">2Dii</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">DFS = disease-free survival; No. = number; QOL = quality of life.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><sup>a</sup>For more information and definition of terms, see text and the <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI Dictionary of Cancer Terms</a> for additional information and definition of terms.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><sup>b</sup>Number of patients treated plus number of patients controlled may not equal number of patients enrolled; number of patients enrolled = number of patients initially recruited/considered by the researchers who conducted a study; number of patients treated = number of enrolled patients who were administered the treatment being studied and for whom results were reported; historical control subjects are not included in number of patients enrolled.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><sup>c</sup>Chemotherapy, radiation therapy, hormonal therapy, or cytokine therapy administered/allowed at the same time as mistletoe therapy.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><sup>d</sup>For information about levels of evidence analysis and scores, see <a href="/books/n/pdqcis/CDR0000256874/?report=reader">Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><sup>e</sup>This was a four-arm trial; patients were randomly assigned to surgery only or to surgery plus radiation therapy, followed by a second randomization to no mistletoe treatment or to treatment with Eurixor; the resulting treatment groups contained the following numbers of evaluable patients: surgery only = 105, surgery plus Eurixor = 97, surgery plus radiation therapy = 137, and surgery plus radiation therapy plus
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Eurixor = 138; radiation therapy and Eurixor treatment overlapped; no treatment approach was superior in terms of disease-free survival, disease-specific survival, improvement in QOL, or stimulation of
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the immune system; in the table, mistletoe-treated and nontreated (control) patients were grouped (i.e., number treated = 97 + 138 = 235, and number control = 105 + 137 = 242).</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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