Abstract

Objective. To evaluate controlled clinical studies on the efficacy and effectiveness of Viscum album for quality of life (QoL) in cancer.

Materials and methods. The authors conducted a search of 7 electronic databases and reference lists and had extensive consultations with experts. They carried out a criteria-based assessment of methodological study quality. Results. The authors identified 26 randomized controlled trials (RCTs) and 10 non-RCTs that investigated the influence of V album extracts (VAEs) on QoL in malignant diseases; 26 studies assessed patient-reported QoL. Questionnaires were mostly well established and validated. Half of the studies investigated VAEs concomitant with chemotherapy, radiotherapy, or surgery. Some studies were well designed, whereas others had minor or major methodological weaknesses. Among the 26 RCTs, 22 reported a QoL benefit, 3 indicated no difference, and 1 did not report any result. All the non-RCTs reported a QoL benefit. Of the studies with higher methodological quality, most reported a benefit, whereas 1 found no difference. Improvements were mainly in regard to coping, fatigue, sleep, exhaustion, energy, nausea, vomiting, appetite, depression, anxiety, ability to work, and emotional and functional well-being in general and, less consistently, in regard to pain, diarrhea, general performance, and side effects of conventional treatments. VAEs were well tolerated.

Conclusions. VAEs seem to have an impact on QoL and reduction of side effects of conventional therapies (chemotherapy, radiation) in experimental trials as well as in routine daily application. The influence on fatigue especially should be investigated further.

Keywords: clinical trials, quality of life, complementary therapies, herbal medicine, Viscum album, mistletoe, neoplasms

Citation: Kienle, G. S., & Kiene, H. (2010). Review Article: Influence of Viscum album L (European Mistletoe) Extracts on Quality of Life in Cancer Patients: A Systematic Review of Controlled Clinical Studies. Integrative Cancer Therapies, 9(2), 142–157. https://doi.org/10.1177/1534735410369673

GS Kienle, F Berrino, A Bussing, E Portalupi, S Rosenzweig, and H Kiene.

Background: Mistletoe preparations are among the most widely used unconventional cancer therapies in Central Europe. Their clinical effectiveness, however is controversial. Objective: To investigate whether prospective, controlled clinical trials provide evidence for efficacy of mistletoe therapy in cancer.

Citation: Kienle, G. S., Berrino, F., Bussing, A., Portalupi, E., & Rosenzweig, S. (2003). Mistletoe in cancer: A systematic review on controlled clinical trials. European Journal of Medical Research, 2003(8), 109–119.

Review: Kienle, G. S., Berrino, F., Bussing, A., Portalupi, E., Rosenzweig, S., & Kiene, H. (2003). Mistletoe in cancer: A systematic review on controlled clinical trials. In Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. Centre for Reviews and Dissemination (UK). https://www.ncbi.nlm.nih.gov/books/NBK69731/

Citation: Huber, R., Schlodder, D., Effertz, C., Rieger, S., & Tröger, W. (2017). Safety of intravenously applied mistletoe extract – results from a phase I dose escalation study in patients with advanced cancer. BMC Complementary and Alternative Medicine, 17(1), 465. https://doi.org/10.1186/s12906-017-1971-1

Purpose: Mistletoe extract (ME) is widely used for patients with cancer to support therapy and to improve quality of life (QoL). However, its use is controversial due to suboptimal trials and a lack of data supporting its intravenous administration.

Materials and Methods: This phase I trial of intravenous mistletoe (Helixor M) aimed to determine the recommended phase II dosing and to evaluate safety. Patients with solid tumor progressing on at least one line of chemotherapy received escalating doses of Helixor M three times a week. Assessments were also made of tumormarker kinetics and QoL.

Results: Twenty-one patients were recruited. The median follow-up duration was 15.3 weeks. The MTD was 600 mg. Treatment-related adverse events (AE) occurred in 13 patients (61.9%), with the most common being fatigue (28.6%), nausea (9.5%), and chills (9.5%). Grade 3+ treatmentrelated AEs were noted in 3 patients (14.8%). Stable disease was observed in 5 patients who had one to six prior therapies. Reductions in baseline target lesions were observed in 3 patients who had two to six prior therapies. Objective responses were not observed. The disease control rate (percentage of complete/partial response and stable disease) was 23.8%. The median stable disease was 15 weeks. Serum cancer antigen-125 or carcinoembryonic antigen showed a slower rate of increase at higher dose levels. The median QoL by Functional Assessment of Cancer Therapy-General increased from 79.7 at week 1 to 93 at week 4.

Conclusions: Intravenous mistletoe demonstrated manageable toxicities with disease control and improved QoL in a heavily pretreated solid tumor population. Future phase II trials are warranted.

Significance: Although ME is widely used for cancers, its efficacy and safety are uncertain. This first phase I trial of intravenous mistletoe (Helixor M) aimed to determine phase II dosing and to evaluate safety. We recruited 21 patients with relapsed/refractory metastatic solid tumor. Intravenous mistletoe (600 mg, 3/week) demonstrated manageable toxicities (fatigue, nausea, and chills) with disease control and improved QoL. Future research can examine ME’s effect on survival and chemotherapy tolerability.

Citation: Paller, C. J., Wang, L., Fu, W., Kumar, R., Durham, J. N., Azad, N. S., Laheru, D. A., Browner, I., Kachhap, S. K., Boyapati, K., Odeny, T., Armstrong, D. K., Meyer, C. F., Gaillard, S., Brahmer, J. R., Page, I., Wang, H., & Diaz, L. A., Jr. (2023). Phase I Trial of Intravenous Mistletoe Extract in Advanced Cancer. Cancer Research Communications, 3(2), 338–346. https://doi.org/10.1158/2767-9764.CRC-23-0002

Et al.= Gaillard, Stephanie; Brahmer, Julie R.; Page, Ivelisse; Wang, Hao; Diaz, Luis A., Jr.