Survival of cancer patients treated with mistletoe extract (Iscador): A systematic literature review

Center for Integrative Medicine, Faculty of Medicine, University of Witten/Herdecke, Herdecke, Germany.
BMC Cancer (Impact Factor: 3.36). 12/2009; 9(1):451. DOI: 10.1186/1471-2407-9-451
Source: PubMed


In Europe, extracts from Viscum album (VA-E), the European white-berry mistletoe, are widely used to treat patients with cancer.
We searched several databases such as Cochrane, EMBASE, NCCAM, NLM, DIMDI, CAMbase, and Medline. Inclusion criteria were controlled clinical studies on parameters associated with survival in cancer patients treated with Iscador. Outcome data were extracted as they were given in the publication, and expressed as hazard ratios (HR), their logarithm, and the respective standard errors using standard formulas.
We found 49 publications on the clinical effects of Iscador usage on survival of cancer patients which met our criteria. Among them, 41 studies and strata provided enough data to extract hazard ratios (HR) and their standard errors (Iscador versus no extra treatment). The majority of studies reported positive effects in favour of the Iscador application. Heterogeneity of study results was moderate (I2 = 38.3%, p < 0.0001). The funnel plots were considerably skewed, indicating a publication bias, a notion which is corroborated by statistical means (AC = -1.3, CI: -1.9 to -0.6, p <= 0.0001). A random effect meta-analysis estimated the overall hazard ratio at HR = 0.59 (CI: 0.53 to 0.66, p < 0.0001). Randomized studies showed less effects than non-randomized studies (ratio of HRs: 1.24, CI: 0.79 to 1.92, p = 0.35), and matched-pair studies gave significantly better results than others (ratio of HRs: 0.33; CI: 0.17 to 0.65, p = 0.0012).
Pooled analysis of clinical studies suggests that adjuvant treatment of cancer patients with the mistletoe extract Iscador is associated with a better survival. Despite obvious limitations, and strong hints for a publication bias which limits the evidence found in this meta-analysis, one can not ignore the fact that studies with positive effects of VA-E on survival of cancer patients are accumulating. Future studies evaluating the effects of Iscador should focus on a transparent design and description of endpoints in order to provide greater insight into a treatment often being depreciated as ineffective, but highly valued by cancer patients.

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    • "Two components of mistletoe, namely, viscotoxins and lectins, have been shown to be largely responsible for these effects [7] [8] [9]. Reports on the clinical efficacy of mistletoe therapy have been conflicting and systematic Evidence-Based Complementary and Alternative Medicine literature reviews often criticise studies for poor design [10] [11]. Although an effect of mistletoe on tumour shrinkage in vivo or overall survival might remain to be proven more thoroughly, a growing number of studies indicate beneficial effects on quality of life of cancer patients and reduction of adverse drug reactions (ADRs) associated with conventional cancer treatments [12] [13] [14] [15] [16] [17]. "

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    • "Viscum album extract has been shown to induce tumor regression by cell cycle apoptosis and activating cell death pathways. Furthermore, it can induce secretion of pro-inflammatory cytokines such as Tumor necrosis factor α, IL 1 and IL6 [7] [12]. So far, however, there has been little research about other species of mistletoe especially Southeast mistletoe. "
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    • "Subsequent preclinical research into mistletoe extracts revealed a multitude of highly interesting compounds (e.g., mistletoe lectins, viscotoxins, alkaloids, triterpenes, and oligo-and polysaccharides ) with antitumoral (cytotoxic, antiangiogenic) as well as immunomodulating properties [3] [4] [5]. Clinical application increased overall survival time and improved quality of life of patients with various forms of cancer [6] [7] [8] and furthermore seemed to be safe [8] [9]. "
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    ABSTRACT: Extracts from European mistletoe (Viscum album L.) developed in anthroposophic medicine are based on specific pharmaceutical procedures to enhance remedy efficacy. One such anthroposophic pharmaceutical process was evaluated regarding effects on cancer cell toxicity in vitro and on colchicine tumor formation in Lepidium sativum. Anthroposophically processed Viscum album extract (APVAE) was produced by mixing winter and summer mistletoe extracts in the edge of a high-speed rotating disk and was compared with manually mixed Viscum album extract (VAE). The antiproliferative effect of VAE/APVAE was determined in five cell lines (NCI-H460, DU-145, HCC1143, MV3, and PA-TU-8902) by WST-1 assay in vitro; no difference was found between VAE and APVAE in any cell line tested (P > 0.14). Incidence of colchicine tumor formation was assessed by measurement of the root/shoot-ratio of seedlings of Lepidium sativum treated with colchicine as well as VAE, APVAE, or water. Colchicine tumor formation decreased after application of VAE (-5.4% compared to water, P < 0.001) and was even stronger by APVAE (-8.8% compared to water, P < 0.001). The high-speed mistletoe extract mixing process investigated thus did not influence toxicity against cancer cells but seemed to sustain morphostasis and to enhance resistance against external noxious influences leading to phenomenological malformations.
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