Mistletoe treatments for minimising side effects of anticancer chemotherapy

BACKGROUND: More than 200,000 persons died in 2002 in Germany as a consequence of cancer diseases. Cancer (ICD-9: 140-208, ICD-10: C00-C97) accounted for 28% of all male deaths and for 22% of all female deaths. Cancer treatment consists on surgery, radio- and chemotherapy. During chemotherapy patients may experience a wide variety of toxic effects (including life-threatening toxicity) which require treatment. The type and the intensity of chemotherapy toxicity are one of the limiting factors in cancer treatment. Toxic effects are also one of the factors affecting health related quality of life (HRQOL) during chemotherapy. Mistletoe extracts belong to the group of so called „unconventional methods“ and are used in Germany as complementary cancer treatments. It has been postulated that the addition of mistletoe to chemotherapeutical regimes could help reduce chemotherapy-induced toxicity and enhance treatment tolerability. The German social health insurance covers the prescription of ML I standardized mistletoe extracts when those are prescribed as palliative cancer treatments with the aim of improving HRQOL. RESEARCH QUESTIONS: Does the addition of mistletoe to chemotherapeutical regimes reduce their toxicity? Does the addition of mistletoe to chemotherapeutical regimes contribute to improve quality of life? Has the addition of mistletoe to chemotherapeutical regimes any effects on survival? Has the addition of mistletoe to chemotherapeutical regimes any effects on tumor-remission? METHODS: We conducted a systematic literature search in following databases: The Cochrane Library, DIMDI Superbase and Dissertation Abstracts. We included systematic reviews and randomized controlled trials (RCT). Appraisal of literature was done by two authors independently. Checklists were used to guide literature appraisal. The Jadad-Score was used to score quality of RCT. Evidence was summarized in tables and in narrative form. RESULTS AND DISCUSSION: The literature search yielded 437 potentially relevant papers. A total of 94 papers was retrieved. Of them, 48 were potentially relevant for answering the research questions and 46 for background information. In this report we summarize the results from three systematic reviews, five published RCT and two unpublished RCT. A protocol of an ongoing systematic review from the Cochrane Collaboration was also identified. The information gathered from the systematic reviews was insufficient to answer the research questions. The relevant studies identified and synthetised in these reviews were appraised and extracted again. In addition, a set of recently published RCT was identified and included in these report. None of the RCT defined frequency or severity of chemotherapy associated toxic effects as its primary outcome. Some of the RCT reported, however, rates of toxic effects or parameters related to toxicity. The results are inconsistent among the RCT ranging from no effect on to positive effects (i. e. reduction) on chemotherapy toxicity. RCT with treatment toxicity as primary outcome are needed to answer the question of whether the addition of mistletoe extracts to chemotherapy regimes can help reducing treatment toxicity. HRQOL was the primary outcome in four RCT. The addition of mistletoe to chemotherapy showed to have a positive effect on HRQOL of women treated for breast cancer. CONCLUSIONS: The available evidence does not allow giving a conclusive answer to the question of whether the addition of mistletoe to chemotherapeutical regimes can reduce the toxicity of the latter. RCT are needed in which the primary outcome is treatment toxicity. The addition of standardised mistletoe extract to chemotherapeutical regimes in the treatment of women with breast cancer can lead to improvements in HRQOL. In the light of the results from RCT the coverage of mistletoe in cancer treatment should be restricted in Germany to the latter indication.