Written by Mirjam Wuesthof and the CAM-Cancer Consortium.
Updated January 19, 2015

Mistletoe (Viscum album)

Does it work ?

Mistletoe is one of the most widely studied complementary and alternative medicine therapies for cancer. Mistletoe extracts have been evaluated in numerous clinical studies and improvements in survival, quality of life, and/or stimulation of the immune system have been frequently reported. However, most clinical studies conducted to date have had one or more major weaknesses that raise doubts about the reliability of the findings.

Systematic reviews and meta-analyses of controlled trials

Several systematic reviews and meta-analyses of more than fifty clinical trials on cancer patients treated with mistletoe extracts have been performed. They are described in table 1. Six systematic reviews published since 2008 addressed multidimemsional measures in terms of improvement of quality of life (QOL), survival, symptom relief and safety in patients with various cancer types 21-26, 28. Most studies reported an improvement in QOL dimensions such as fatigue, sleep, appetite, anxiety, nausea, pain as well as general physical, emotional and functional wellbeing (Table 1). Weaknesses of controlled trials include small numbers of participants, failure to adequately document drop-outs, use of inadequate randomization procedures and absence of treatment blinding. Oxford quality scoring (Jadad scale) repeatedly led to poor scores, mostly because of absence of treatment blinding. This represents a difficult to solve challenge for clinical trials as the mistletoe treatment usually induces dermal erythema at injection site, therefore the value of blinding may be questionable. 

A 2012 meta-analysis of 9 RCTs and 4 non-RCTs revealed some evidence that Iscador® treatment might have moderate beneficial effect on QoL in various cancer types. 21 Limitations were heterogeneous data and poor methodological quality of included trials.

A 2010 systematic review examined 26 RCTs and 10 non-RCTs.22 A total of 22 RCTs  and all 10 non-RCTs reported an improvement in QOL. Improvement in fatigue, nausea and vomiting, emotional well-being, and concentration were reported. Some of the studies were well designed, while others showed weaknesses.

Another 2010 systematic review investigated QOL, survival, tumour response and safety.23 A total of 19 RCTs, 16 non-RCTs and 11 cohort studies with heterogeneous end points were included. Consistent improvement of QOL dimensions fatigue, sleep, appetite, anxiety, nausea, pain as well as general physical, emotional and functional wellbeing  were seen in 21 of 24 trials assessing QOL. Beneficial effects on survival were documented in 12 of 22 trials assessing survival and on tumour response in 3 of 6 trials assessing tumour response. The methodological quality of the studies differed substantially, although some of the more recent studies, especially on quality of life, were reasonable well conducted.

A systematic review from 2009 included 18 trials (RCTs and non-RCTs) 24. It confirmed the insufficient evidence in terms of overall survival, but indicated positive effects on quality of life characteristic values, such as increased appetite, better sleep, less fatigue and improvement of general physical and psychological wellbeing. The authors concluded that the quality of the studies was mostly low. Finally, the authors were unable to identify marked differences between various preparations and advocate the use of the umbrella term "mistletoe therapy" for all of them.

Pooled analysis was performed within a 2009 meta-analysis of 22 trials with different designs by Ostermann et al. 25 Effects on survival in favour of Iscador® versus no treatment were reported. But there was evidence of publication bias and, when focussing on just randomised studies only, the effect was no longer significant.

In a 2008 Cochrane review of 21 RCTs of various cancers tumour response, QOL, and psychological distress were evaluated 26. Survival times were included in 13 of the studies, six of them showed benefits. 14 of 16 studies reported beneficial effects for QOL such as improvement of performance index, symptom scales and psychological measures, although studies where limited by several methodological weaknesses. The two placebo-controlled studies on QOL found significant superiority over placebo. The authors concluded that “the evidence from RCTs to support the view that the application of mistletoe extracts has impact on survival or leads to an improved ability to fight cancer or to withstand anticancer treatments is weak”. Earlier warnings about a potential negative effect of adjuvant treatment with Iscador® in melanoma patients could not be proven but also no benefit could be shown in one trial performed by the EORTC Melanoma Group 27. Nevertheless, there is some evidence that mistletoe extracts may offer benefits on measures of QOL during chemotherapy for breast cancer, but these results need replication.

Overall, more high-quality, independent clinical research is needed to truly assess the safety and effectiveness of mistletoe extracts. Patients receiving mistletoe therapy should be encouraged to take part in future trials 26.

Controlled trials

Four recent RCTs on cancer patients were published after the most recent systematic reviews (Table 2). In general the methodological quality of the newer trials has improved, but the studies still have some limitations. All trials investigating efficacy found various outcome parameters significantly improved. Comprehensive and conclusive assessments are still difficult to draw.

A randomized phase II trial involving 72 patients with previously untreated advanced non-small cell lung cancer investigated the influence of Iscador® on chemotherapy-related side effects and QOL.28 Chemotherapy dose reductions, severe non-hematologic side effects and rates of hospitalization were less frequent in patients treated with Iscador®. There was no statistically significant difference in any of the items of the questionnaires. Therefore, no definite conclusion of a possible effect of Iscador® on quality of life and total adverse events could be drawn by the authors.

A Korean pilot RCT evaluated the effect of AbnobaViscum® Q on chemotherapy related adverse events, QOL and safety in 32 patients with gastric cancer parallel to adjuvant treatment with doxofluridine (a 5FU pro-drug).29 Significantly improved diarrhoea was seen in the mistletoe arm. The overall QOL item “global health status” significantly improved while the specific QoL parameters (physical-, emotional-, cognitive-, social- and  role function) did not improve significantly.

A recent phase III randomized trial involving 220 patients with locally advanced or metastatic pancreatic cancer, not eligible for chemotherapy, investigated the effect of mistletoe extract (Iscador® Qu) versus best supportive care on overall survival.30 Median overall survival was significantly improved (4.8 months in the mistletoe arm and 2.7 months in control arm). A prognosis-group adjusted hazard ratio of 0.49 (p <0.0001) was estimated.

Citation

Mirjam Wuesthof, CAM-Cancer Consortium. Mistletoe (Viscum album) [online document]. http://cam-cancer.org/The-Summaries/Herbal-products/Mistletoe-Viscum-album. January 19, 2015.

Document history

Summary fully revised and updated in January 2015 by Mirjam Wuesthof.

Summary first published in March 2011, authored by Edzard Ernst.

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