For many people, mistletoe conjures up images of Christmas holidays, but in parts of Europe, mistletoe extract is widely used as a therapy for cancer patients. However, a new review of studies finds only weak evidence that the treatment provides any benefit.
Mistletoe proponents believe it strengthens the immune system while minimizing the side effects of chemotherapy and radiation therapy, thereby improving survival and increasing quality of life during treatment. In 2002, mistletoe extract was the most frequently prescribed therapy in German outpatient cancer clinics, outstripping tamoxifen.
The compound is not approved for use in the United States to treat any medical condition, including cancer.
While the plant contains several biologically active substances that could kill cancer cells, fight viruses and tune the immune system, how these substances work is still not clearly understood and there is much debate about whether they work at all in oncology therapy, according to Dr. Markus Horneber, lead review author. Horneber is a member of the Work Group for Biological Cancer Treatment based in Nuremberg, Germany.
The researchers looked at whether mistletoe extract could increase survival times, enhance the response of tumors to therapy, improve quality of life and alleviate the adverse effects of anti-cancer drugs. The team also evaluated the safety of mistletoe extracts.
The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates research in all aspects of health care. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing trials on a topic.
The review included 21 randomized clinical trials that used the extract either as the sole therapy or as an adjunct to chemotherapy or radiation. The studies comprised 3,484 cancer patients from Austria, Bulgaria, China, Germany, Italy, Romania, Russia and Ukraine.
There was little standardization in procedure, patient groups, outcome measures or the mistletoe compounds or doses used, the reviewers found. “The general reporting of [randomly controlled trials] was poor,” they wrote.
It is particularly challenging to standardize herbal medicine studies, according to Eric Manheimer, a research associate for the University of Maryland Center for Integrative Medicine.
“Mistletoe grows on a tree, so the exact components of the medication might depend on the species of tree it’s grown on, or the growing season,” said Manheimer, who was not associated with the review.
Other factors can complicate herbal medicine studies, the reviewers noted. Because consumers can purchase herbal remedies over the counter, it might be hard to find study participants with no previous exposure to the substance. Moreover, the dose and frequency of mistletoe extract, which is injected under the skin, depends on the patient’s initial reaction.
In the 13 studies that investigated how long patients survived, six showed some benefit; but again, the authors noted that the methodology of all of these studies was of low quality. Of the 16 studies that looked at quality of life, reduction of symptoms or reduced side effects from chemotherapy, 14 showed some benefit, but the authors found only two of these studies to have higher-quality methodology.
There was no evidence of side effects or adverse reactions to the mistletoe extract.
Manheimer said that small, nontraditional journals - many of which are not peer-reviewed - published most of the studies, so they are not comparable to major clinical trials. It can be difficult to get funding for trials of herbal preparations, he said. “In general, companies don’t have the same profit motive with herbal medicine as they do with proprietary chemicals.” He noted that companies selling mistletoe extract supported most of the studies in the review.
While the data supporting mistletoe’s benefits are weak, “nevertheless, there is some evidence that mistletoe extracts may offer benefits on measures of [quality of life] during chemotherapy for breast cancer, but these results need replication,” the reviewers concluded.
Because there is no firm evidence of the efficacy of mistletoe therapy, said Manheimer, “its use would depend on the expert judgment of the clinician and other practical considerations, and the preferences of the patient.”
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The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org for more information.
Horneber MA, et al. Mistletoe therapy in oncology (Review). Cochrane Database of Systematic Reviews 2008, Issue 2.
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