Cancer patients are understandably desperate and leave no stone unturned to improve their prognosis. Thus they become easy prey of charlatans who claim that this or that alternative therapy will cure them or improve their outlook. One of the most popular alternative cancer therapies is mistletoe, a treatment dreamt up by Rudolf Steiner on the basis of the ‘like cures like’ principle: the mistletoe plant grows on a host tree like a cancer in the human body. One of many websites on this subject, for instance, states:
- integrates with conventional cancer treatments
- can be used for a wide range of cancers
- may be started at any stage of the illness….
- Improved quality of life
- generally feeling better
- increased appetite and weight
- less tired/more energy
- reduced pain
- better sleep pattern
- felling more hopeful and motivated
- reduced adverse effects from chemo and radiotherapy
- reduced risk of cancer spread and recurrence
- increased life expectancy.
Mistletoe extracts have been shown in studies to:
- stimulate the immune system
- cause cancer cell death
- protect healthy cells against harmful effects of radiation and chemotherapy.
In fact, the debate about the efficacy of mistletoe either as a cancer cure, a supportive therapy, or a palliative measure is often less than rational and seems never-ending.
The latest contribution to this saga comes from US oncologists who published a phase I study of gemcitabine (GEM) and mistletoe in advanced solid cancers (ASC). The trial was aimed at evaluating: (1) safety, toxicity, and maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3) formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma concentrations, (5) clinical response, and (6) pharmacokinetics of GEM.
A total of 44 study participants were enrolled; 20 were treated in stage I (mistletoe dose escalation phase) and 24 in stage II (gemcitabine dose escalation phase). All patients had stage IV disease; the majority had received previous chemo-, hormonal, immunological, or radiation therapy, and 23% were chemotherapy-naïve.
Patients were treated with increasing doses of a mistletoe-extract (HELIXOR Apis (A), growing on fir trees) plus a fixed GEM dose in stage I, and with increasing doses of GEM plus a fixed dose of mistletoe in stage II. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery.
The results show that dose-limiting toxicities were neutropenia, thrombocytopenia, acute renal failure, and cellulitis, attributed to mistletoe. GEM 1380 mg/m2 and mistletoe 250 mg combined were the MTD. Of the 44 patients, 24 developed non-neutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation.
6% of patients showed a partial response, and 42% had stable disease. Of the 44 study participants, three died during the study, 10 participants requested to terminate the study, 23 participants progressed while on study, one terminated the study due to a dose limiting toxicity, 6 left due to complicating disease issues which may be tied to progression, and one voluntarily withdrew.
An attempt was made to follow study subjects once they terminated study treatment until death. At the last attempt to contact former participants, three were still alive and five others were lost to follow-up. The median time to death of any cause was approximately 200 days. Compliance with mistletoe injections was high.
The authors explain that a partial response rate of 6% is comparable to what would be expected from single agent gemcitabine in this population of patients with advanced, mostly heavily pretreated carcinomas. The median survival from study enrollment of about 200 days is within the range of what would be expected from single agent gemcitabine.
The authors concluded that GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone.
These results are hardly encouraging but they originate from just one (not particularly rigorous) study and might thus not be reliable. So, what does the totality of the reliable evidence tell us? Our 2003 systematic review of 10 RCTs found that 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.
Will this stop the highly lucrative trade in mistletoe extracts? will it prevent desperate cancer patients being misled about the value of mistletoe treatment? I fear not.
Rudolf Steiner was a weird guy by any stretch of imagination. He was the founding father of anthroposophy, an esoteric “philosophy” that created a new dimension of obtrusiveness. Not only that, he also dabbled in farming methods, devised an educational technique and created an entire school of health care, called anthroposophical medicine. The leading product in its range of homeopathy-inspired “drugs” is a mistletoe-extract which is, according to Steiner, a cure for cancer. His idea was simple: the mistletoe plant is a parasite that lives off host trees sapping its resources until, eventually, it might even kill its host – just like cancer threatening the life of a human being!!!
So, what is more logical than to postulate that extracts from mistletoe are a cure for cancer? Medicine seems simple – particularly, if you do not understand the first thing about it!
But here comes the odd thing: some ingredients from mistletoe do actually have anti-cancer properties. So, was the old Steiner an intuitive genius who somehow sensed that mistletoe would be a life-saver for cancer patients? Or is all this just pure luck? Or was it perhaps predictable?
Many plants produce molecules that are so toxic that they can kill (cancer) cells, and many conventional cancer drugs were originally derived from plants; the fact that mistletoe has some anti-cancer activity therefore comes as a surprise only to those who have little or no knowledge of phyto-pharmacology.
Ok, mistletoe might have some ingredients which possess pharmacological activity. But to claim that it is a cancer cure is still a huge leap of faith. This fact did not stop promoters of anthroposophical medicine to do just that.
Due to decades of clever promotion, it is now hard in many countries (including for instance Germany) to find cancer patients who have not tried mistletoe; indeed, selling mistletoe preparations to desperate cancer patients has become a mega-business.
But does it actually work? Do these extracts achieve what proponents advertise?
The claims for mistletoe are essentially twofold:
1) Mistletoe cures cancer.
2) Mistletoe improves the quality of life (QoL) of cancer patients.
The crucial question clearly is: are these claims based on good evidence?
According to our own systematic review, the answer is NO. In 2003, we looked at all the clinical trials and demonstrated that 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. The current Cochrane review (of which I am not a co-author) concluded similarly : 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.
But both reviews have one major weakness: they included all of the many available extracts of mistletoe – and one cannot deny that there are considerable differences between them. The market leader in this area is Weleda (avid readers of science blogs might remember that this firm has been mentioned before); they produce ISCADOR, the mistletoe extract that has been tested more than any other such preparation.
Perhaps it would be informative to focus specifically on this product then? A German team from the “Center for Integrative Medicine, Faculty of Health, University of Witten/Herdecke” has done just that; despite the fact that these authors are not really known for their critical analyses of anthroposophical medicine, their conclusion is also cautious: The analyzed studies give some evidence that Iscador treatment might have beneficial short-time effects on QoL-associated dimensions and psychosomatic self-regulation.
So, what is the bottom line? Sceptics would say that almost a century of research without a solid proof of efficacy is well and truly enough; one should now call it a day. Proponents of mistletoe treatment, however, insist: we need more and better studies. Well, there is more! A new RCT of Iscador has just been published.
It included chemotherapy-naive advanced non-small-cell lung cancer (NSCLC) patients to assess Iscador’s influence on chemotherapy-related adverse-effects and QoL. Patients with advanced NSCLC were randomised to receive chemotherapy alone or chemotherapy plus Iscador thrice weekly until tumour progression. Chemotherapy consisted of 21-day cycles of carboplatin combined with gemcitabine or pemetrexed. Seventy-two patients were enrolled of whom 65% were in stage IV, and 62% had squamous histology. Median overall survival in both groups was 11 months. Median time to tumour progression was not significantly different between the two groups. Differences in grade 3-4 haematological toxicity were not significant, but more control patients had chemotherapy dose reductions, grade 3-4 non-haematological toxicities, and hospitalisations.
The authors’ conclusion: No effect of Iscador could be found on quality of life or total adverse events. Nevertheless, chemotherapy dose reductions, severe non-haematological side-effects and hospitalisations were less frequent in patients treated with Iscador, warranting further investigation of Iscador as a modifier of chemotherapy-related toxicity.
So, does Steiner’s notion based on the weirdest of intuitions contain some kernel of truth? I am not sure. But for once I do agree with the proponents of mistletoe: we need more and better research to find out.