Research and clinical studies are important

for developments in mistletoe therapy.

Read about case reports, clinical trials and systematic reviews.

We have a small selection of the most up to date reports, trials and reviews on mistletoe therapy. If you are interested in finding out more about specific cancers, you can also visit the German Mistel Die research website.


April 2017: Mistletoe & breast cancer pilot randomised controlled trial 
We are very pleased to announce that a pilot randomised controlled trial for mistletoe therapy in the UK has been given the go ahead. Find out more including how to support the research by visiting the campaign page.

UPDATED: Mistletoe Therapy and Cancer - an Overview 2017

Produced by a research team at the University of Witten/Herdecke, this paper summarises all the recent evidence on Mistletoe Therapy with regards to safety, effectiveness and impact on Quality of Life and Life Expectancy.

This is useful reading for those who wish to gain an oversight of mistletoe evidence available.

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Case Studies

Complete remission and long-term survival of a patient with melanoma metastases treated with high-dose fever-inducing Viscum album extract: A case report

Werthmann PG, Hintze A, Kienle GS
Medicine. Oct 2017; 96:46(e8731).

Introduction: Metastatic malignant cutaneous melanoma (MCM)-a highly immunogenic cancer-typically has a poor prognosis. Viscum album extracts (VAEs) have strong immune-stimulating, apoptogenic, and cytotoxic effects.
Case Presentation: A 66-year-old MCM patient with newly diagnosed lymph node metastases opted for sole VAE treatment. VAEs were initially applied subcutaneously, and then later in exceptionally high, fever-inducing doses, both intravenously and intralesionally. The metastases shrunk over the following months, and after 2 years, all lesions had completely remitted (regional and hilar lymph nodes). The patient has been tumor free for 3.5 years at the time of publication (and for 5 years since initiation of intensified VAE treatment). Besides fever and flu-like symptoms, no side effects occurred.
Discussion: We presume that VAE triggered an increased release of tumor-associated antigens, enhanced immunologic recognition, and increased immune response against the tumor tissue and induced tumor remission.

Please contact Mistletoe Therapy UK, if you would like a copy of the full paper.

The case for mistletoe in the treatment of laryngeal cancer

Shakeel M, Trinidade A, Geider S, Ah-See KW
The Journal of Laryngology & Otology. March 2014; 128: 302–306.

Introduction: Complementary and alternative medicine usage, though rising, remains largely devoid of a sound scientific basis; however, there is increasing evidence to support its use in cancer therapy.
Aim: To present the case of a patient with laryngeal carcinoma who made a full recovery following mistletoe therapy, despite failing to respond to chemoradiotherapy and salvage laryngectomy.
Design: Case report with relevant literature review.
Results: The patient developed extensive, unresectable stomal recurrence, and it was deemed appropriate to supply palliative care only. Following treatment with mistletoe extract injections after palliative radiotherapy, he recovered fully and was eventually discharged from care.
Conclusion: The benefit of mistletoe in laryngeal cancer treatment requires further investigation, and might be considered in selected patients, as an adjunct or when other conventional therapies have failed.

Please contact Mistletoe Therapy UK, if you would like a copy of the full paper.

Durable Regression of primary Cutaneous B-Cell Lymphoma Following Fever-inducing Mistletoe treatment: Two Case Reports

Orange M, Lace A, Fonseca MP, von Laue BH, Geider S & Kienle GS.
Global Advances in Health and Medicine. March 2012 1(1): 18-25

Background: Mistletoe is a complementary cancer treatment that is widely used, usually in addition to and alongside recommended conventional cancer therapy. However, little is known about its use, effectiveness, and safety in the treatment of cutaneous lymphoma.
Case Report: Two patients with primary cutaneous B-cell lymphoma (pT2bcNxM0 follicle center and pT2ac-NxM0 marginal zone) either declined or postponed recommended conventional treatment and received high-dose, fever-inducing mistletoe treatment; a combination of intratumoral, subcutaneous, and intravenous application was given; and one patient also underwent whole-body hyperthermia. The lymphoma regressed over a period of 12 and 8 months, respectively, and after administration of a cumulative dose of 12.98 g and 4.63 g mistletoe extract, respectively. The patients are in remission to date, 3.5 years after commencement of treatment. Neither patient received conventional cancer treatment during the entire observation period.

Please contact Mistletoe Therapy UK, if you would like a copy of the full paper.

Durable tumour responses following primary high dose induction with mistletoe extracts: Two case reports

Orange M, Fonseca A, Lace A, von Laue HB & Geider S
European Journal of Integrative Medicine, June 2010; 2(2): 63–69

Introduction: Viscum album L. extracts (VAEs) are widely used in the complementary treatment of cancer, to improve quality of life of cancer patients, commonly using subcutaneous application of low doses of VAEs.
Case presentations: Two patients were treated with VAE (AbnobaViscum®) alone, using a combination of intratumoural, subcutaneous and in one case intravenous administration. A 75-year-old lady with relapsed Merkel cell cancer – a rare and aggressive neuro-endocrine cancer of the skin – declined radiotherapy, and was treated with VAE alone over 9.8 months, using a total of 5.8G VAE, averaging 592 mg/VAE/month (>300,000 ng mistletoe lectin (ML)/month; >2300 μg viscotoxin (VTX)/month); the 3 cm tumour was impalpable after 4 months and she continues to be in complete remission after 3 years. A 50-year-old postmenopausal woman with asynchronous bilateral breast cancer (right breast: grade 1, hormone sensitive; left breast: grade 3, hormone insensitive and HER2-positive ductal carcinoma), declined all conventional cancer treatment. She was treated with VAE alone for 2.6 years, with a total of 8.9G VAE, averaging 290 mg/month (>150,000 ng ML/month; >1200 μg VTX/month); she had complete responses of both tumours after 31 months of intratumoural and subcutaneous VAE application, and remains in remission after 4 years.
Conclusions: Durable tumour regression occurred in 2 patients following treatment with VAE, used in higher than generally used doses and combining different applications. Both patients had no other established cancer therapies. Further studies are required to define the strategic role of VAE and its different applications, safety and efficacy.

Please contact Mistletoe Therapy UK, if you would like a copy of the full paper.


Clinical Trials

Viscum album L. extract therapy in patients with locally advanced or metastatic pancreatic cancer: A randomised clinical trial on overall survival

Tröger W, Galun D, Reif M, Schumann A, Stankovic N, Milicevic M
European Journal of Cancer. Dec 2013; 49(18): 3788-97

Background: The unfavourable side-effects of late-stage pancreatic cancer treatments call for non-toxic and effective therapeutic approaches. We compared the overall survival (OS) of patients receiving an extract of Viscum album [L.] (VaL) or no antineoplastic therapy.
Methods: This is a prospective, parallel, open label, monocentre, group-sequential, randomised phase III study. Patients with locally advanced or metastatic cancer of the pancreas were stratified according to a binary prognosis index, composed of tumour stage, age and performance status; and were evenly randomised to subcutaneous injections of VaL extracts or no antineoplastic therapy (control). VaL was applied in a dose-escalating manner from 0.01 mg up to 10mg three times per week. Patients in both groups received best supportive care. The primary end-point was 12-month OS, assessed in a group-sequential analysis.
Findings: We present the first interim analysis, including data from 220 patients. Baseline characteristics were well balanced between the study arms. Median OS was 4.8 for VaL and 2.7 months for control patients (prognosis-adjusted hazard ratio, HR=0.49; p<0.0001). Within the 'good' prognosis subgroup, median OS was 6.6 versus 3.2 months (HR=0.43; p<0.0001), within the 'poor' prognosis subgroup, it was 3.4 versus 2.0 months respectively (HR=0.55; p=0.0031). No VaL-related adverse events were observed.
Conclusion: VaL therapy showed a significant and clinically relevant prolongation of OS. The study findings suggest VaL to be a non-toxic and effective second-line therapy that offers a prolongation of OS as well as less disease-related symptoms for patients with locally advanced or metastatic pancreatic cancer.

Please contact Mistletoe Therapy UK, if you would like a copy of the full paper.

Health services research of integrative oncology in palliative care of patients with advanced pancreatic cancer

Axtner J, Steele M, Kröz M, Spahn G, Matthes H, Schad F
BMC Cancer 2016; 16: 579

Background: Pancreatic cancer has a dire prognosis and is associated with a high mortality. Palliative patients have special needs and often seek help in integrative oncological concepts (IO) that combine conventional and complementary therapies. Nevertheless there are few recommendations regarding IO in current cancer guidelines. The aims of this study were to report on implementation of IO in everyday palliative care and to analyze patient survival in advanced pancreatic cancer.
Methods: This multicenter observational study investigates the implementation of IO and length of survival of patients suffering from advanced pancreatic cancer (stage IV). We analyzed patient’s survival by employing multivariable proportional hazard models using different parametric distribution functions and compared patients receiving chemotherapy only, a combination of chemotherapy and Viscum album (VA) treatment, and VA treatment only.
Results: Records of 240 patients were analyzed. Complementary therapy showed high acceptance (93 %). Most frequent therapy was VA treatment (74 %) that was often administered concomitantly to chemotherapy (64 %). Both therapies had positive effects on patient survival as they had significant negative effects on the hazard in our log-normal model. A second analysis showed that patients with combined chemotherapy and VA therapy performed significantly better than patients receiving only chemotherapy (12.1 to 7.3 month). Patients receiving only VA therapy showed longer survival than those receiving neither chemotherapy nor VA therapy (5.4 to 2.5 months). Our data demonstrates that IO can be implemented in the everyday care of patients without disregarding conventional treatment. Patients combining VA with chemotherapy showed longest survival.
Conclusions: Our data demonstrate the importance and potential of health services research showing that IO treatment can be successfully implemented in the every-day care of patients suffering from advanced pancreatic cancer. Patients combining VA with chemotherapy showed longest survival. To address patients’ needs adequately, future cancer guidelines might increasingly include comments on complementary treatment options in addition to conventional therapies. Further studies should investigate the effect of complementary treatments on survival and quality of life in more detail.

Please contact Mistletoe Therapy UK, if you would like a copy of the full paper.

Quality of Life of Patients With Advanced Pancreatic Cancer During Treatment With Mistletoe: A randomized controlled trial

Tröger W, Galun D, Reif M, Schumann A, Stankovic N, Milicevic M
Dtsch Arztebl Int 2014; 111(29-30): 493-502

Background: The treatment of cancer patients with mistletoe extract is said to prolong their survival and, above all, improve their quality of life. We studied whether the quality of life of patients with advanced pancreatic cancer could be improved by mistletoe extract.
Methods: An open, single-center, group-sequential, randomized phase III trial (ISRCTN70760582) was conducted. From January 2009 to December 2010, 220 patients with locally advanced or metastatic pancreatic cancer who were receiving no further treatment for pancreatic cancer other than best supportive care were included in this trial. They were stratified by prognosis and randomly allocated either to a group that received mistletoe treatment or to one that did not. Mistletoe extract was given in escalating doses by subcutaneous injection three times a week. The planned interim evaluation of data from 220 patients indicated that mistletoe treatment was associated with longer overall survival, and the trial was terminated prematurely. After termination of the study, the results with respect to quality of life (assessed with the QLO-C30 scales of the European Organisation for Research and Treatment of Cancer) and trends in body weight were evaluated.
Results: Data on quality of life and body weight were obtained from 96 patients treated with mistletoe and 72 control patients. Those treated with mistletoe did better on all 6 functional scales and on 7 of 9 symptom scales, including pain (95% confidence interval [CI] −29 to –17), fatigue (95% CI –36.1 to –25.0), appetite loss (95% CI −51 to −36.7), and insomnia (95% CI –45.8 to –28.6). This is reflected by the trend in body weight during the trial.
Conclusion: In patients with locally advanced or metastatic pancreatic carcinoma, mistletoe treatment significantly improves the quality of life in comparison to best supportive care alone. Mistletoe is an effective second-line treatment for this disease.

Please contact Mistletoe Therapy UK, if you would like a copy of the full paper.


Systematic Reviews

Mistletoe therapy in oncology

Horneber M, Bueschel G, Huber R, Linde K, Rostock M.
Cochrane Database of Systematic Reviews. April 2008, (2): CD003297

Background: Mistletoe extracts are commonly used in cancer patients. It is claimed that they improve survival and quality of life (QOL) in cancer
Objectives: To determine the effectiveness, tolerability and safety of mistletoe extracts given either as monotherapy or adjunct therapy for patients
with cancer.
Main Results: Eighty studies were identified. Fifty-eight were excluded for various reasons, usually as there was no prospective trial design with randomised treatment allocation. Of the 21 included studies 13 provided data on survival, 7 on tumour response, 16 on measures of QOL or psychological outcomes, or prevalence of chemotherapy-related adverse effects and 12 on side effects of mistletoe treatment; overall comprising 3484 randomised cancer patients. Interventions evaluated were 5 preparations of mistletoe extracts from 5 manufacturers and one commercially not available preparation. The general reporting of RCTs was poor. Of the 13 trials investigating survival, 6 showed some evidence of a benefit, but none of them was of high methodological quality. The results of two trials in patients with melanoma and head and neck cancer gave some evidence that the used mistletoe extracts are not effective for improving survival. Of the 16 trials investigating the efficacy of mistletoe extracts for either improving QOL, psychological measures, performance index, symptom scales or the reduction of adverse effects of chemotherapy, 14 showed some evidence of a benefit, but only 2 of them including breast cancer patients during chemotherapy were of higher methodological quality. Data on side effects indicated that, depending on the dose, mistletoe extracts were usually well tolerated and had few side effects.
Author's Conclusions: 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. 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 trails.

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Influence of Viscum album L (European mistletoe) extracts on quality of life in cancer patients: a systematic review of controlled clinical studies.

Kienle GS, Kiene H.
Integrative Cancer Therapy. June 2010; 9(2):142-157.

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

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Complementary cancer therapy: a systematic review of prospective clinical trials on anthroposophic mistletoe extracts.

Kienle GS, Kiene H.
European Journal of Medical Research. March 2007; 12(3):103-119.

Background: Anthroposophic Mistletoe therapy is a widely used complementary cancer treatment.
Objective: To evaluate prospective clinical trials on the effectiveness of anthroposophic mistletoe therapy for cancer.
Design: Systematic review.
Material & methods: Search of 9 electronic databases, reference lists and extensive expert consultations. Criteria-based assessment of methodological study quality.
Results: 16 randomized (RCT) and 9 non-randomized (N-RCT) controlled trials were identified that investigated mistletoe treatment of malignant diseases. Statistically significant benefit for survival was reported in 8 of 17 trials (in 5 of 10 RCTs), for disease-free survival and tumour recurrence in none of 2 RCTs, for remission of tumour and malignant effusion in 1 RCT and 1 N-RCT of 4 controlled trials, for quality of life (QoL) in 3 of 5 RCTs, and for QoL and reduction of side effects of cytoreductive therapies (chemotherapy, radiation or surgery) in 5 of 7 trials (3 of 5 RCTs). Methodological quality of the controlled trials differed substantially; some had major limitations while others were reasonably well conducted. 12 single-arm cohort studies were identified. 5 of 7 studies found substantial tumour remission in various cancers, one study reported remission of CIN, and 4 studies remission of malignant pleural effusion or ascites. Quality of reporting in cohort studies was mostly reasonably good. Mistletoe application was well tolerated.
Conclusions: Regarding quality of studies and consistency of results, the best evidence for efficacy of mistletoe therapy exists for improvement of QoL and reduction of side effects of cytotoxic therapies (chemotherapy, radiation). Survival benefit has been shown but not beyond critique. Tumour remissions are described in cohort studies that investigate the application of high dose or local mistletoe extracts. As several reasonably well-conducted studies indicate beneficial effects, further properly designed trials should be encouraged to investigate clinical efficacy and its possible dependency on the mode of application.

Please contact Mistletoe Therapy UK, if you would like a copy of the full paper.


Safety Studies

Clinical safety of combined therapy of immune checkpoint inhibitors and Viscum album L/. therapy in patients with advanced or metastatic cancer

Thronicke A., Steele M., Grah C., Matthes B., Schad F.
BMC Complementary and Alternative Medicine. 2017

Despite improvement of tumour response rates in patients with progressive and metastatic cancer, immune checkpoint inhibitors (ICM) induce toxicities in cancer patients. Viscum album L. (VA, mistletoe) extracts are applied as add-on cancer therapy especially in German speaking countries and within integrative and anthroposophical concepts with the goal to improve quality of life. The primary objective of this pilot observational cohort study was to determine the rate of adverse events (AE) related to ICM therapy with and without VA in patients with advanced or metastatic cancer in a certified Cancer Center.
ICM or combined ICM/VA therapies were applied in patients with progressive or metastatic cancer. AE rates of both therapy groups were compared.
A total of sixteen cancer patients were treated with ICM: nivolumab (75%), ipilimumab (19%) or pembrolizumab (6%). The median age of the study population was 64 years (IQR 57.8; 69.3); 44% were male. Of the sixteen patients receiving ICM, nine patients received additional VA (56%; ICM/VA group) and seven did not (44%; ICM group). No statistically significant differences were seen between groups with respect to AE-rates (67% ICM/VA versus 71% ICM). Adjusted multivariate regression analysis revealed that concomitant application of VA did not alter the AE rate in ICM treated patients. 85% of AEs were expected ICM reactions. No AEs of grade 3 or greater were documented for the total study cohort.
This is the first study evaluating the clinical safety profile of ICM in combination with VA in patients with advanced or metastatic cancer. The overall AE rate of the study cohort is comparable to AE rates of ICM treatment in the literature. Our data indicate a first impression that concomitant VA application may not alter ICM-induced AE rates. However, the nature of this study does not allow excluding possible immunological interactions between ICM and VA. Further prospective trials in larger study cohorts should focus on the assessment of safety aspects, clinical efficacy and health related quality of life in patients with combined ICM/VA therapy.

Please contact Mistletoe Therapy UK, if you would like a copy of the full paper.

Immune-related and adverse drug reactions to low versus high initial doses of Viscum album L. in cancer patients

Schad F., Thronicke A., Merkle A., Matthes H., Steele M.
Phytomedicine 36. 2017, p54-58

Background: Immune-related adverse drug reactions (ADRs) to immunotherapy agents have been associated with beneficial clinical outcomes in oncology. Viscum album L. (VA, European mistletoe) is frequently used as an immunomodulatory agent alongside conventional cancer treatment in Europe. VA has been associated with
improved quality of life and a reduction in chemotherapy-related ADRs. Beneficial effects of VA are believed to be related to its immunomodulatory properties. Current guidelines recommend commencing with a low dose and increasing slowly overtime, however, off-label prescribing of high initial doses is common.
We investigated ADR profiles related to subcutaneous VA therapy commencing with low, recommended doses versus higher than recommended doses.
Study Design: Retrospective cohort study.
Medical records of 1361 cancer patients treated between 2003 and 2013 were assessed. Patients were divided into two groups based on whether the dose of their first VA injection adhered to current guidelines. Patient characteristics and suspected VA-related ADRs were compared between dose groups.
Of 1361 cancer patients, 516 (38%) started with a recommended, low dose of VA(≤0.02 mg) and 845 (62%) started with a higher dose(>0.02 mg). Groups did not differ by age or gender, but significant differences were observed for type (p<0.001) and stage of cancer (p=0.05). Starting with a high dose of VA was significantly
associated with a higher incidence of VA-related ADRs compared to starting with a low dose (20.7% versus 0.8%, p<0.001). Adjusting for age, gender, tumour type and stage of disease, produced an odds ratio of 37.5 (95% CI=15.7–122.8, p<.001). Almost all ADRs, irrespective of the initial VA dose, were of mild or moderate intensity. Most ADRs were immune-related, general disorders and administration site conditions, many of which are desired reactions, such as pyrexia and local reactions. Overall, no serious ADRs occurred. 
Starting VA therapy with a higher than recommended dose was associated with a high frequency of ADRs, however, nearly all ADRs were expected, of mild to moderate intensity and most were desired reactions. Future research is necessary to investigate whether higher incidences of immune-related events are indicators of beneficial immunomodulation and better clinical outcomes.

Please contact Mistletoe Therapy UK, if you would like a copy of the full paper.