MD, PhD, FMedSci, FRSB, FRCP, FRCPEd.

Mistletoe treatment of cancer patients was the idea of Rudolf Steiner. Mistletoe grows on a host tree like a parasite and eventually might kill it. This seems similar to a cancer killing a patient, and Steiner – influenced by the homeopathic ‘like cures like’ notion – thought that mistletoe should thus be an ideal treatment of all cancers. Despite the naivety of this concept, it somehow did catch on, and mistletoe has now become the number one cancer SCAM in Europe which is spreading fast also to the US and other countries.

But, as we all know, the fact that a therapy lacks plausibility does not necessarily mean that it is clinically useless. To decide, we need clinical trials; and to be sure, we need rigorous reviews of all reliable trials. Two such papers have just been published.

The aim of the systematic review was to give an extensive overview about current state of research concerning mistletoe therapy of oncologic patients regarding survival, quality of life and safety.

The authors extensive literature searches identified 3647 hits and 28 publications with 2639 patients were finally included in this review. Mistletoe was used in bladder cancer, breast cancer, other gynecological cancers (cervical cancer, corpus uteri cancer, and ovarian cancer), colorectal cancer, other gastrointestinal cancer (gastric cancer and pancreatic cancer), glioma, head and neck cancer, lung cancer, melanoma and osteosarcoma. In nearly all studies, mistletoe was added to a conventional therapy. Patient relevant endpoints were overall survival (14 studies, n = 1054), progression- or disease-free survival or tumor response (10 studies, n = 1091). Most studies did not show any effect of mistletoe on survival. Especially high quality studies did not show any benefit.

The authors concluded that, with respect to survival, a thorough review of the literature does not provide any indication to prescribe mistletoe to patients.

The aim of the second systematic review by the same team was to give an extensive overview about the current state of evidence concerning mistletoe therapy of oncologic patients regarding quality of life and side effects of cancer treatments. The same studies were used for this analysis as in the first review. Regarding quality of life, 17 publications reported results. Studies with better methodological quality showed less or no effects on quality of life.

The authors concluded that with respect to quality of life or reduction of treatment-associated side effects, a thorough review of the literature does not provide any indication to prescribe mistletoe to patients with cancer.

In 2003, we published a systematic review of the same subject. Here is its abstract:

Mistletoe extracts are widely used in the treatment of cancer. The results of clinical trials are however highly inconsistent. We therefore conducted a systematic review of all randomised clinical trials of this unconventional therapy. Eight databases were searched to identify all studies that met our inclusion/exclusion criteria. Data were independently validated and extracted by 2 authors and checked by the 3rd according to predefined criteria. Statistical pooling was not possible because of the heterogeneity of the primary studies. Therefore a narrative systematic review was conducted. Ten trials could be included. Most of the studies had considerable weaknesses in terms of study design, reporting or both. Some of the weaker studies implied benefits of mistletoe extracts, particularly in terms of quality of life. None of the methodologically stronger trials exhibited efficacy in terms of quality of life, survival or other outcome measures. Rigorous trials of mistletoe extracts fail to demonstrate efficacy of this therapy.

As we see, 16 years and 18 additional trials have changed nothing!

I therefore think that it is time to call it a day. We should stop the funding for further research into this dead-end alley. More importantly, we must stop giving false hope to cancer patients. All that mistletoe therapy truly does is to support a multi-million Euro industry.

7 Responses to Mistletoe treatment for cancer is useless and should be discouraged

  • Will giving up mistletoe therapy threaten the livelihood of the druid Panoramix (Getafix in the English translations) in the Asterix books? I think it is a key ingredient in his magic potion.

    The more I hear/read about the Steiner legacy the more damaging he becomes. Apparently Waldorf schools, at least in the USA, are quite anti-vax.

  • I am so sad to see this come out. Have you reviewed their methodology? There were over 2000 articles left after removing duplicates and of those they only considered 30 RCT for their review. That is a mere 1% of the available articles. They went through these in a two month period. How can they be sure they included all the relevant trials? Non-randomized trials can also be valid trials, but they are making broad sweeping recommendations without including any of those and they are also discounting the human reported findings in many of the trials they eliminated. They didn’t address the low side effects or toxicity from Mistletoe therapy, or the fact that it doesn’t interfere with traditional treatment. In this article https://www.ncbi.nlm.nih.gov/pubmed/15630849 they state the overall contribution of curative and adjuvant cytotoxic chemotherapy to 5-year survival in adults was estimated to be 2.3% in Australia and 2.1% in the USA and yet they didn’t recommend that doctors stop prescribing cytotoxic drugs which are proven to cause lasting harmful side effects. I am guessing you didn’t publish these findings with a title of ‘Cytotoxic drugs are useless and should be discouraged.”

    As a current person with cancer whose traditional chemotherapy treatment failed, FOFLOX6 with MRI showing wide spread metastasis 1 month after stopping treatment, it is disheartening to see researchers claim that the perpetuation of the use of Mistletoe and other complementary treatments gives patients false hope. I also have a mutation that shows many of the traditional second line treatments don’t work for me. Should I go curl up in my bed now and wait to die? Or maybe I should spend my remaining days sick from other traditional treatments with the ‘true hope’ that it MIGHT work based on the more accurate pharmaceutical funded research that says it might? Perhaps preventing me from quality time with loved ones?

    There are very few clear answers with regard to cancer treatment both allopathic and complementary. I do wish researchers and sites like yours would be more careful with their recommendations for both sides.

    2018 – currently open https://www.hopkinsmedicine.org/kimmel_cancer_center/research_clinical_trials/clinical_trials/mistletoe.html

    2016 – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860234/
    2014 – mhttp://cancerres.aacrjournals.org/content/74/19_Supplement/3206
    2010 – https://www.ncbi.nlm.nih.gov/pubmed/20483874

    • I think you need to learn about research methodology and differentiate reliable from less reliable evidence. the authors of this review did a good job and it is not their fault that you fail to understand the complexity of the issues involved. this article might be a good start:
      https://edzardernst.com/2012/11/what-is-and-what-isnt-clinical-evidence-and-why-is-the-distinction-important/

      • Wow. You have discounted me right out of the gate and my ability to comprehend the complexity of clinical research. Thank you for making my point. It is complex and there is bias at almost every turn with clinical trials and even systematic reviews. Why would you feel the need to shut me down? So others will not question this or any other research you agree with? Isn’t that what scientists and researchers do: question? everything?

        In the article in question, in the Toxicity section under Chemotherapy- the authors state “Most of the studies found some positive effects of mistletoe treatment concerning toxicity of chemotherapy.” They then go on to describe the studies and the results, which were statistically relevant.

        From this standpoint, I think the recommendation that mistletoe is useless and should not be used is incorrect and warrants further research. Chemo toxicity is a major issue for most patients. For the authors, and you, to completely discount it even when the review shows otherwise is irresponsible.

        I have read your post from the link you sent and have a few questions based on your comments:

        Your comment:
        The multifactorial nature of any clinical response requires controlling for all the factors that might determine the outcome other than the treatment per se. Ideally, we would need to create a situation or an experiment where two groups of patients are exposed to the full range of factors, and the only difference is that one group does receive the treatment, while the other one does not. And this is precisely the model of a controlled clinical trial.
        Such studies are designed to minimise all possible sources of bias and confounding. By definition, they have a control group which means that we can, at the end of the treatment period, compare the effects of the treatment in question with those of another intervention, a placebo or no treatment at all.

        My question:
        Can you please direct me to human clinical trials with 200 or more participants where all factors other than the prescribed treatment were the same for every person in each group – including prescriptions for co-morbidities, diet, sleep, supplements, environmental factors, etc. Where researchers can guarantee that each group behaved and performed exactly the same outside of the hours they were receiving the clinical trial treatment?

        Your comment:
        Causality is the key in all of this; and here lies the crucial difference between clinical experience and scientific evidence. What clinician witness in their routine practice can have a myriad of causes; what scientists observe in a well-designed efficacy trial is, in all likelihood, caused by the treatment. The latter is evidence, while the former is not.

        Don’t get me wrong; clinical trials are not perfect. They can have many flaws and have rightly been criticised for a myriad of inherent limitations. But it is important to realise that, despite all their short-commings, they are far superior than any other method for determining the efficacy of medical interventions.

        My question:
        Exactly, clinical trials are not perfect. How is a systematic review free from the same types of flaws and bias since it is reviewing the studies as they exist, including their flaws?

        Your comment:
        Unfortunately, the findings of these replications do not always confirm the results of the previous study. Whenever we are faced with conflicting results, it is tempting to cherry-pick those studies which seem to confirm our prior belief – tempting but very wrong. I
        In order to arrive at the most reliable conclusion about the efficacy of any treatment, we need to consider the totality of the reliable evidence. This goal is best achieved by conducting a systematic review.

        My question:
        How can the reader of the review be assured the reviewers had no bias and did not cherry-pick the articles that confirm to their beliefs?

        Your comment:
        In a systematic review, we assess the quality and quantity of the available evidence, try to synthesise the findings and arrive at an overall verdict about the efficacy of the treatment in question.

        Technically speaking, this process minimises selection and random biases. Systematic reviews and meta-analyses [these are systematic reviews that pool the data of individual studies] therefore constitute, according to a consensus of most experts, the best available evidence for or against the efficacy of any treatment.

        My question:
        How does this minimise selection and random bias, when every person has some form of bias?

        • I did not say that my post answers all the questions; I said IT’S A START.
          if you seriously want to understand research methodology, you have to do quite a bit more.
          alternatively, you trust those experts who have gone through this process.

    • I, too, have an incurable malignancy. I am also an oncologist, and I have seen first-hand the damage that can result from belief in the false promises of alternative medicine.

      I have had a look at the papers that you quote, and it seems to me that you haven’t really understood them.

      https://www.ncbi.nlm.nih.gov/pubmed/15630849
      Unfortunately this was published by Elsevier, which means that unless you have a subscription or institutional access (which I no longer have now that I have had to give up working due to ill health) you have to pay to read the full paper. Having said that, the abstract is familiar and I think I did read the paper some time last year.

      The authors give the figures of 2.1% in the USA and 2.3% in Australia as being the absolute proportion of people with a cancer diagnosis in whom they attribute their five-year survival to chemotherapy alone. To understand these numbers, we need to know what proportion of new cancer diagnoses were treated with chemotherapy at all. Certainly not everybody with cancer receives chemotherapy, and if only those were included then the proportion benefiting would be much higher. In Australia, for instance, malignant melanoma is common, and it is usually treated with minor surgery alone.

      It is also important to consider why the chemotherapy was given. If the cancer was deemed incurable at the time of diagnosis, then the chemotherapy may well have been given in order to relieve symptoms, or in the hope of prolonging survival from, say, six months, to two years. This is a real and important benefit, but would not show in five-year survival figures.

      This study was of patients diagnosed in 1998. Given the enormous changes in cancer treatment over the course of my career, this is not really representative of current practice.

      Let me give you the example of prostate cancer. This is one of the commonest cancers and would have made up a significant proportion of the patients in the study. For a long time it was regarded as very poorly responsive to chemotherapy. However, a large international trial published results (in 2014 or 2015 I think) showing that patients with metastatic prostate cancer at the time of diagnosis who were given chemotherapy with docetaxel as part of their initial treatment lived nearly two years longer than those treated with hormones alone (although they were allowed chemotherapy later on if they relapsed). This has led to a complete change in practice in this patient group.

      https://www.hopkinsmedicine.org/kimmel_cancer_center/research_clinical_trials/clinical_trials/mistletoe.html
      This refers to a clinical trial which is currently ongoing, and is not evidence of efficacy of the treatment under evaluation, which will have to wait until the trial has been completed and published. Clinical trials such as this are the only proper setting for otherwise unproven interventions.

      http://cancerres.aacrjournals.org/content/74/19_Supplement/3206
      Unfortunately there was a typo in your post meaning that the hyperlink doesn’t work. I cut and pasted the URL into my brower and found an in vitro study of cancer cells in culture. While this is interesting, it is not a test of an actual treatment in a cancer patient. In vitro studies are an essential part of drug testing, but only a tiny fraction of agents found to have a potentially beneficial effect in this sort of experiment ever turn out to be clinically useful.

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860234/
      This gives the results of a questionnaire issued to anthroposophic practitioners (as invented by Rudolf Steiner); it would be surprising if they didn’t endorse mistletoe.

      https://www.ncbi.nlm.nih.gov/pubmed/20483874
      From the abstract alone (I can’t find the full paper) it is impossible to know whether the randomised trials were blinded. If not then the findings may well have been due to the placebo effect. I note that the author was also one of the co-authors of the anthroposophic questionnaire study, and that it was published in the same dodgy journal.

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