Mistletoe in Cancer – Clinical Studies – Overview

Clinical effectiveness of mistletoe extracts in the treatment of oncological disease has been investigated in a number of studies: 30 prospective randomised controlled trials, 18 non-randomised prospective comparative studies and 42 retrospective comparative studies primarily investigated the impact of mistletoe treatment (anthroposophic preparations) on disease course (like survival, tumor behaviour or quality of life) in comparison to other treatments (or to no additional treatment). 40 cohort studies and case series have primarily addressed the questions: How frequently does tumour remission occur during a particular mistletoe treatment? What is the overall impact of mistletoe treatment on general health (pre-post comparisons)? - Each of these research methodologies have their own specific advantages and limitations. Each type of study requires relevant expertise and accurate implementation, and can only be interpreted in relation to its informational value.

At present there is a trend to recognise and endorse only large randomised controlled trials (RCTs) and to strongly devalue other types of studies in comparison. Under ideal conditions, RCTs are indeed consummate—but in relation to everyday clinical reality they present numerous limitations. The RCT prioritisation process gives rise to numerous distortions in public health care (for example, as a result of commerce bias, career bias, bias of ‘large numbers’, mediocrity bias, bias as a result of therapy priority) and also leads to considerable discrepancies between research and everyday medical practice, to ethical problems and to divergent, asymmetrical results (see: Necessity for pluralistic evaluation methods). Hence it makes sense to generate a synthesis of information drawn from different kinds of evidence—rather than limiting the scope to RCTs alone. [1]

Characteristically, mistletoe studies are not only carried out by pharmaceutical companies and academic institutions, but also to an unusually high degree by practicing doctors who are motivated, out of their own initiative, to investigate mistletoe therapy or special applications for it, and to publish and discuss their observations. While this indicates a high degree of commitment and practice-orientated research, these studies often lack the formal methodological and technical standards that large research institutions with their commensurate infrastructure and financial strength are able to provide .

There are to date 130 clinical studies (searching strategy) (two further studies were excluded on the basis of inconsistencies; details see [4-8]) on the therapeutic effectiveness of anthroposophical mistletoe preparations (Abnobaviscum^®, Helixor, Iscador^®, Iscar, Iscucin^®, Isorel^®) in tumour patients (selection criteria) with respect to

• survival (34 prospective comparative studies, 2 cohort studies, 39 retrospective comparative studies),
• tumour regression (4 prospective comparative studies, 32 cohort studies, 1 retrospective comparative study),
• disease-free interval, recurrence (11 prospective comparative studies, 3 retrospective comparative studies),
• reducing the side-effects of conventional tumour treatments (chemotherapy, radiation therapy, surgery) (10 prospective comparative studies, 1 cohort study, 4 retrospective comparative studies),
• Quality of Life, disease-related symptoms (16 prospective comparative studies, 19 cohort studies, 5 retrospective comparative studies),
• hospitalization (2 retrospective comparative studies).

With regards to method, these were

• 48 prospective comparative studies (30 of which were randomised trials),
• 40 cohort studies /case series with pre-post design (18 prospective, 17 retrospective, 5 unclear),
• 42 retrospective comparative studies with comparison group (5 of which were retrolective).

These studies examined the mistletoe treatment of

• gynaecological tumours (breast cancer, ovarian cancer, cervix carcinoma, cervical dysplasia, various genital cancers),
• gastrointestinal tumours (cancer of the intestine, liver tumours, colorectal cancer, stomach cancer, pancreas tumours, liver metastases),
• tumours of the airways (lung cancer, ENT-Tumours),
• skin cancer (melanoma, anal condyloma),
• haematological malignancies (non-Hodgkin-lymphoma, various lymphoma, multiple myeloma, CML, myelodysplasia),
• malignant exudates (ascites, pleural effusion, pericardial effusion),
• urogenital tumours (renal cell cancer, prostate cancer, bladder cancer),
• brain tumours,
• various tumours.

Clinical trials concerning immunomodulation as a result of mistletoe therapy and tolerance and safety have not been considered in this review and are evaluated separately.

The clinical trials have been critically assessed with regard to methodological quality [2–6]. As different aspects are emphasised in each type of trial, it is necessary to apply different quality assessment criteria . The methodological quality of the studies under review varies considerably. Many of the prospective studies (comparative and non-comparative) have been carefully conducted and comprehensively published. Especially among the retrospective comparative trials several had major shortcomings, particularly because comparability was often questionable; only a few studies had adjusted for most important baseline differences to improve comparability. Two recently published pharmacoepidemiological retrolective trials achieved markedly better methodological quality through careful and extensive data collection and appropriate statistical methods for adjustment of baseline differences.

The results of the clinical studies predominantly report benefits to using mistletoe therapy. With regard to quality of studies and consistency of results, the best evidence concerning efficacy of mistletoe therapy exists for the improvement of quality of life and improved tolerability of cytoreductive therapies (chemotherapy, radiotherapy, surgery). Also well-substantiated is the observation that tumour remission can be induced through the injecting of mistletoe extracts. This finding is consistent with the preclinical research regarding substantial cytotoxicity and treatment of tumours in animals. However, such tumour remissions appear to be dependent upon dosage and method of administration: With respect to the customary low-dose mistletoe therapy, tumour remissions are rare exceptions. A benefit in survival time due to mistletoe treatment is possible. This might depend on the duration of the mistletoe therapy, in addition to factors relating to dosage, host tree and choice of preparation. Highly individualised and comprehensive treatment - individually adjusted and selected dosage, preparations, host tree, injection site and rhythm of administration, and supplementation with other interventions - are regarded to lead to far better health outcomes. These considerations are brought forward by practicing doctors referring to their observations and to plausible biological, oncological and clinical arguments. However, systematic research assessing the benefit of this highly individualised treatment is lacking and by its very nature, this subject cannot be satisfactorily elucidated by the generally accepted types of clinical trial. [1]

Gunver S. Kienle, MD
Last Update:
August 2010

References

[1] Kienle, G. S., Gibt es Gründe für Pluralistische Evaluationsmodelle? Limitationen der Randomisierten Klinischen Studie. Z ärztl Fortbild Qual Gesundh wes 99, 289-294 (2005).

[2] Kienle, G. S., F. Berrino, A. Büssing, E. Portalupi, S. Rosenzweig and H. Kiene, Mistletoe in cancer - a systematic review on controlled clinical trials. Eur J Med Res 8, 109-119 (2003).

[3] Kienle, G. S. and H. Kiene, Die Mistel in der Onkologie - Fakten und konzeptionelle Grundlagen. Schattauer Verlag, Stuttgart, New York (2003).

[4] Kienle, G. S. and H. Kiene, Complementary Cancer Therapy: A Systematic Review of Prospective Clinical Trials on Anthroposophic Mistletoe Extracts. Eur J Med Res 12, 103-119 (2007). Download of the original article

[5] Kienle, G. S., A. Glockmann, M. Schink and H. Kiene, Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research. J Exp Clin Cancer Res 28, 79-112 (2009). Download of the original article

[6] Kienle, G.S. and H. Kiene, Influence of Viscum album L (Eurepean Milstletoe) Extracts on Quality of Life in Cancer Patient: A Systematic Review of Controlled Clinical Studies. Integrative Cancer Therapies 9(2) 142-157 (2010).
DOI: 10.1177/1534735410369673 Download of the original article

[7] Kienle, G. S., Kiene, H. and Albonico, H. U., Health Technology Assessment Bericht Anthroposophische Medizin. Erstellt im Rahmen des Programm Evaluation Komplementärmedizin (PEK) des Schweizer Bundesamtes für Sozialversicherung (2005). Download of the HTA-report in German: www.ifaemm.de

[8] Kienle, G. S., H. Kiene and H. U. Albonico, Anthroposophic Medicine: Effectiveness, Utility, Costs, Safety. Schattauer Verlag, Stuttgart, New York (2006).