MD, PhD, FMedSci, FSB, FRCP, FRCPEd

quality of life

You have to excuse me, if I keep coming back to this theme: so-called ‘alternative cancer cures’ are truly dangerous. I have tried to explain this already many times, for instance here, here and here. And it is by no means just alternative therapists who make a living of such quackery. Sadly qualified medical doctors are often involved as well. As to prove my point, here is a tragic story that broke yesterday:

Former Miss New Hampshire, Rachel Petz Dowd, lost her battle with cancer on Sunday 12 June 2016 — a battle she fought publicly through personal writings in a blog in hopes of helping others on a similar journey toward healing. The singer/songwriter and mother of three from Auburn died about a month after traveling to Mexico for an aggressive form of alternative cancer treatment. She turned 47 last week. Dowd was diagnosed with stage 2 triple negative breast cancer in May 2014. The diagnosis led her to create a blog called “Rachel’s Healing” to document what she hoped would be a journey back to health. “I hope my readers can gain something from my journey and that they find their own personal way to combat this disease impacting too many women today,” she wrote. Dowd used the blog to share her experiences with traditional and natural medicine during her cancer fight.

On 5/3/16 Mrs Dowd wrote on her blog: “Well after some careful consideration and looking at different clinics and hospitals we’ve made a decision. Will be going to the CMN Hospital on the Yuma, Arizona border*. For 28 days of treatments. It’s not a day clinic but a full hospital servicing over the past 30 years. There’s a special wing dedicated to alternative cancer care and the treatment list is impressive.  Many treatments that are not available in this country. We feel this would be the best course of care daily for 28 days and then at the end of the 4 weeks I intend my immune system to be back on-line. I will be doing a stem cell boost of my bone marrow the last week. I know of a women, Shannon Knight, from The Truth About Cancer documentary, who had stage 4 metastasized into locations of her bones and her lungs and she came out of there completely cured. Her oncologist said it was nothing short of a miracle, but she said no it was just clean hard work!  She said no it was just clean the hard, aggressive treatments that only attack cancer, boost and prime your immune system, become a whole, healthy being once again:) It is possible and I am planning on being one of the exceptions like Shannon!”

  • The hospital is across the US border in Mexico; it is run by medically qualified personnel.

The hospital [“CMN Hospital’s facility is only 14 blocks away once you cross the border to begin your alternative cancer treatment”] has a website where they tell a somewhat confusing story about their treatment plans; here is a short but telling excerpt:

CMN’s protocols are individualized and comprehensive. You will benefit from oxidative therapies, IV minerals selenium and bicarbonate IV vitamins such as vitamin B-17 and IV vitamin C. Far infrared and others including MAHT, Cold Laser Therapy, Hyperbaric Oxygen Therapy and Ozone Therapy are a daily part of your protocol. Ultraviolet Blood Irradiation is effective in destroying pathogens in your blood and slows the growth of cancer cell growth. CMN’s Stem cell therapy and Dendritic cell therapy are just two of the advanced cancer treatments applied to patients.”

And here is what they say about three therapies as examples of treatments that have discussed before on this blog: vitamin C, Laetrile and Essiac.

IV Vitamin C If large amounts of vitamin C are presented to cancer cells, large amounts will be absorbed. In these unusually large concentrations, the antioxidant vitamin C will start behaving as a pro-oxidant as it interacts with intracellular copper and iron. This chemical interaction produces small amounts of hydrogen peroxide. Because cancer cells are relatively low in an intracellular anti-oxidant enzyme called catalase, the high dose vitamin C induction of peroxide will continue to build up until it eventually lyses the cancer cell from the inside out!

IV Vitamin B17 / Laetrile Also known as amygdaline, Vitamin B-17 is a molecule made up of four parts: -2 parts Glucose -1 part Benzaldahyde-1 part Hydrogen Cyanide. Laetrile is found in at least 1200 different plants, including apricots, peaches, apple seeds, lentils, cashews, brown rice, millet, and alfalfa. Commercial preparations of laetrile are obtained from the kernels of apricots, peaches and bitter almonds. The body requires an enzyme called beta-glucosidase in order to process laetrile and release the cyanide. Studies have shown that cancer cells contain more of this enzyme than normal cells, which allows for a higher release of cyanide at tumor sites. Another enzyme known as rhodanese is important in this process. Normal healthy cells contain rhodanese which protects them from the activated cyanide. Most cancer cells are deficient in this enzyme, leaving them vulnerable to the poison. Tumor destruction begins once the cyanide is released within the malignancies, meaning laetrile therapy is selectively toxic to cancer cells while remaining non-toxic to normal cells.

Essiac Tea / Order Original Essiac Tea Essiac, given its name by Rene Caisse (“caisse” spelt backwards), consists of four main herbs that grow in the wilderness of Ontario, Canada. The original formula is believed to have its roots from the native Canadian Ojibway Indians. The four main herbs that make up Essiac are Burdock Root, Slippery Elm Inner Bark, Sheep Sorrel and Indian Rhubarb Root. Essiac tea helps release toxins that build up in fat and tissues into the blood stream where they can be filtered and excreted by the liver and kidneys.  Cleaning the body of toxins and impurities frees up the immune system to focus on killing cancer cells and protecting the body.

 

I think I will abstain from further comments, firstly because I want to avoid getting sued by these people and secondly because it seems all too depressingly obvious.

Many cancer patients use mistletoe extracts either hoping to cure their cancer or to alleviate its symptoms. The evidence that mistletoe treatment (MT) can achieve either of these goals is mixed but, on the whole, however, it is not positive. Our own systematic review of 2003 concluded that ‘rigorous trials of mistletoe extracts fail to demonstrate efficacy of this therapy’. The more recent Cochrane review concurred: ‘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.’

Patients’ experiences of side effects and the acceptability, tolerability, and perceived benefits of MT have not been assessed critically. The aim of this new article was to systematically review and synthesise the results of qualitative studies of cancer patients’ experiences of using MT.

Electronic searches were conducted in MEDLINE, Embase, PsychLIT, CINAHL, and AMED to identify all qualitative studies of MT. Articles were screened independently by two reviewers and critically appraised using the Critical Appraisal Skills Programme tool. A thematic synthesis of the findings was carried out.

One hundred and seventy-three papers were identified; 156 were excluded at initial screening. Seventeen papers were read in full, 14 of which were excluded. Three articles about patients’ experiences of MT alongside conventional treatment were included in the synthesis, either as a monotherapy (two articles) or as part of a package of anthroposophic treatment (one article). Patients reported demonstrable changes to their physical, emotional, and psychosocial well-being following MT, as well as a reduction in chemotherapy side effects. Self-reported side effects from MT were few, and the studies suggest good adherence to the therapy. Self-injection gave patients a sense of empowerment through involvement in their own treatment.

The authors concluded that ‘given the variation in context of MT delivery across the articles, it is not possible to ascribe changes in patients’ quality of life specifically to MT.’

This might be a polite way of saying that there is no good evidence to suggest that MT positively affects patients’ experiences of side effects and the acceptability, tolerability, and perceived benefits.

Mistletoe is, of course, the ‘flagship’ intervention of Rudolf Steiner’s anthroposophical medicine. About a century ago, his idea was simple (or should this be ‘simplistic’?): 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. It follows, according to the homeopathy-inspired Steiner and the many followers of his cult that mistletoe is an effective cancer therapy.

Despite the weirdness of this concept and the largely negative evidence, MT is hugely popular as a cancer cure, particularly in German-speaking countries. The question I ask myself is this: ISN’T IT TIME THAT THIS NONSENSE STOPS?

Alternative medicine (AM) use has become popular among patients with cancer. I find this very easy to understand: faced with such a grave diagnosis, who would not be tempted to try everything that is being promoted as being helpful. And, by Jove, promoted it is! But does it do any good?

The evidence clearly shows that no form of AM is capable of changing the natural history of any form of cancer. This means the millions of websites that imply otherwise are criminally wrong and frightfully dangerous.

But some AMs might still be useful, namely for improving symptoms, well-being and quality of life (QOL) as supportive or palliative therapies. Unfortunately the evidence for this assumption is less sound than AM fans try to make us believe. Before this background, better research is needed and more trials would be welcome. A brand-new paper might tell us more.

The purposes of this study were to compare the QOL in CAM users and non-CAM users and to determine whether AM use influences QOL among breast cancer patients during chemotherapy.

A cross-sectional survey was conducted at two outpatient chemotherapy centers. A total of 546 patients completed the questionnaires on AM use. QOL was evaluated based on the European Organization for Research and Treatment of Cancer (EORTC) core quality of life (QLQ-C30) and breast cancer-specific quality of life (QLQ-BR23) questionnaires.

A total of 70.7% of patients were identified as AM users. There was no significant difference in global health status scores and in all 5 subscales of the QLQ C30 functional scales between AM users and non-AM users. On the QLQ-C30 symptom scales, AM users (44.96±3.89) had significantly (p = 0.01) higher mean scores for financial difficulties than non-AM users (36.29±4.81). On the QLQ-BR23 functional scales, AM users reported significantly higher mean scores for sexual enjoyment (6.01±12.84 vs. 4.64±12.76, p = 0.04) than non-AM users. On the QLQ-BR23 symptom scales, AM users reported higher systemic therapy side effects (41.34±2.01 vs. 37.22±2.48, p = 0.04) and breast symptoms (15.76±2.13 vs. 11.08±2.62, p = 0.02) than non-AM users. Multivariate logistic regression analysis indicated that the use of CAM modality was not significantly associated with higher global health status scores (p = 0.71).

The authors drew the following conclusions: While the findings indicated that there was no significant difference between users and non-users of AM in terms of QOL, AM may be used by health professionals as a surrogate to monitor patients with higher systemic therapy side effects and breast symptoms. Furthermore, given that AM users reported higher financial burdens (which may have contributed to increased distress), patients should be encouraged to discuss the potential benefits and/or disadvantages of using AM with their healthcare providers.

One needs to caution, of course, that this was not an RCT, and therefore cause and effect cannot be taken for granted. Nevertheless, I believe, that these findings should make us think critically about the wide-spread notion that the supportive and palliative use of AM leads to an improvement of QOL in cancer patients.

This is a question which I have asked myself more often than I care to remember. The reason is probably that, in alternative medicine, I feel surrounded by so much dodgy research that I simply cannot avoid asking it.

In particular, the co-called ‘pragmatic’ trials which are so much ‘en vogue’ at present are, in my view, a reason for concern. Take a study of cancer patients, for instance, where one group is randomized to get the usual treatments and care, while the experimental group receives the same and several alternative treatments in addition. These treatments are carefully selected to be agreeable and pleasant; each patient can choose the ones he/she likes best, always had wanted to try, or has heard many good things about. The outcome measure of our fictitious study would, of course, be some subjective parameter such as quality of life.

In this set-up, the patients in our experimental group thus have high expectations, are delighted to get something extra, even more happy to get it for free, receive plenty of attention and lots of empathy, care, time, attention etc. By contrast, our poor patients in the control group would be a bit miffed to have drawn the ‘short straw’ and receive none of this.

What result do we expect?

Will the quality of life after all this be equal in both groups?

Will it be better in the miffed controls?

Or will it be higher in those lucky ones who got all this extra pampering?

I don’t think I need to answer these questions; the answers are too obvious and too trivial.

But the real and relevant question is the following, I think: IS SUCH A TRIAL JUST SILLY AND MEANINGLESS OR IS IT UNETHICAL?

I would argue the latter!

Why?

Because the results of the study are clearly known before the first patient had even been recruited. This means that the trial was not necessary; the money, time and effort has been wasted. Crucially, patients have been misled into thinking that they give their time, co-operation, patience etc. because there is a question of sufficient importance to be answered.

But, in truth, there is no question at all!

Perhaps you believe that nobody in their right mind would design, fund and conduct such a daft trial. If so, you assumed wrongly. Such studies are currently being published by the dozen. Here is the abstract of the most recent one I could find:

The aim of this study was to evaluate the effectiveness of an additional, individualized, multi-component complementary medicine treatment offered to breast cancer patients at the Merano Hospital (South Tyrol) on health-related quality of life compared to patients receiving usual care only. A randomized pragmatic trial with two parallel arms was performed. Women with confirmed diagnoses of breast cancer were randomized (stratified by usual care treatment) to receive individualized complementary medicine (CM group) or usual care alone (usual care group). Both groups were allowed to use conventional treatment for breast cancer. Primary endpoint was the breast cancer-related quality of life FACT-B score at 6 months. For statistical analysis, we used analysis of covariance (with factors treatment, stratum, and baseline FACT-B score) and imputed missing FACT-B scores at 6 months with regression-based multiple imputation. A total of 275 patients were randomized between April 2011 and March 2012 to the CM group (n = 136, 56.3 ± 10.9 years of age) or the usual care group (n = 139, 56.0 ± 11.0). After 6 months from randomization, adjusted means for health-related quality of life were higher in the CM group (FACT-B score 107.9; 95 % CI 104.1-111.7) compared to the usual care group (102.2; 98.5-105.9) with an adjusted FACT-B score difference between groups of 5.7 (2.6-8.7, p < 0.001). Thus, an additional individualized and complex complementary medicine intervention improved quality of life of breast cancer patients compared to usual care alone. Further studies evaluating specific effects of treatment components should follow to optimize the treatment of breast cancer patients. 

The key sentence in this abstract is, of course: complementary medicine intervention improved quality of life of breast cancer patients… It provides the explanation as to why these trials are so popular with alternative medicine researchers: they are not real research but they are quite simply promotion! The next step would be to put a few of those pseudo-scientific trials together and claim that there is solid proof that integrating alternative treatments into conventional health care produces better results. At that stage, few people will bother asking whether this is really due to the treatments in questioning or to the additional attention, pampering etc.

My question is ARE SUCH TRIALS ETHICAL?

I would very much appreciate your opinion.

Reiki healers believe they are able to channel ‘healing energy’ into patients’ body and thus enable them to get healthy. If Reiki were not such a popular treatment, one could brush such claims aside and think “let the lunatic fringe believe what they want”. But as Reiki so effectively undermines consumers’ sense of reality and rationality, I feel a responsibility to inform the public what Reiki truly amounts to.

This pilot study compared the effects of Reiki therapy with those of companionship on improvements in quality of life, mood, and symptom distress in cancer patients receiving chemotherapy. Thirty-six breast cancer patients received one of three treatments:

  1. usual care,
  2. Reiki + usual care,
  3. companionship + usual care.

First, data were collected from patients receiving usual care. Second, patients were randomized to either receive Reiki or a companionship during chemotherapy.

Questionnaires assessing quality of life, mood, symptom distress, and Reiki acceptability were completed at baseline and chemotherapy sessions 1, 2, and 4.

The results show that Reiki was rated relaxing with no side effects. Reiki and companionship groups both reported improvements in quality of life and mood that were greater than those seen in the usual care group.

The authors concluded that interventions during chemotherapy, such as Reiki or companionship, are feasible, acceptable, and may reduce side effects.

Yet another example of utterly bizarre conclusions from a fairly straight forward study and quite clear results. What they really demonstrate is the fact that Reiki is nothing more than a placebo; its perceived benefit relies entirely on non-specific effects. This view is also supported by our systematic review (its 1st author is a Reiki healer!): the evidence is insufficient to suggest that reiki is an effective treatment for any condition. Therefore the value of reiki remains unproven.

In other words, we do not need a trained Reiki master, nor the illusion of some mysterious ‘healing energy’. Simple companionship without woo or make-believe has exactly the same effect without undermining rationality. Or, to put it much more bluntly: REIKI IS NONSENSE ON STILTS.

One alternative therapy that I have so far neglected on this blog is the Alexander Technique (AT). Actually, it was not really meant to become an alternative therapy when it was first discovered.

F.M. Alexander (1869-1955), an Australian actor, often experienced chronic laryngitis while performing. As his doctors could not help him, he developed a solution on his own. He found that excess muscular tension in his neck and body were causing his problems, and began to experiment on new ways to speak and move with greater ease. His health improved to such an extent that he decided to teach others what he had learned. Over a career span of more than fifty years, he refined his methods. After teaching for over 35 years, he began to train teachers of the ‘Alexander Technique’.

As used in alternative medicine, AT is an educational method aimed at increased sensory awareness and kinesthetic control to modify postural and movement patterns which might be associated with musculoskeletal problems. Proponents claim AT works for a range of conditions, including:

It has been suggested that AT is effective for chronic low back pain; however, so far only one recent study has determined its effects on chronic non-specific neck pain.

In this randomized controlled trial, patients were randomly allocated to either 5 weekly sessions of AT, heat pack application (HEAT) or guided imagery (GI). The primary outcome measure  was the neck pain intensity on a 100-mm visual analogue scale at week 5. Secondary outcomes included neck disability, quality of life, satisfaction and adverse effects. Analyses of covariance were applied on an intention-to-treat population testing ordered hypotheses AT vs. HEAT and AT vs. GI.

A total of 72 patients were included, and 52 of them received all 5 interventions. No significant group difference was found for neck pain intensity when AT was compared to HEAT. However, an exploratory analysis revealed superiority of AT over GI. Significant group differences were also found for physical quality of life in favor of AT vs. HEAT or GI. Adverse events mainly related to slightly increased pain and muscle soreness. AT patients reported increased body awareness and control over the body, relaxing or stimulating effects and mood changes after the sessions.

The authors conclude that 5 sessions of AT were no better than a heat pack application for relieving chronic non-specific neck pain. Therefore it cannot be recommended as routine intervention at this time. Since exploratory analysis revealed some improvements of AT further trials are warranted for conclusive judgment.

One of the most irritating things with alternative medicine research, in my view, is the phenomenon that researchers tend to be quasi-religious advocates of the treatment they investigate. This seems to compel them all too often to extrapolate beyond reason and to drawing conclusions which are way too optimistic, frequently to an extend that borders on scientific misconduct. It is therefore a real pleasure to find an article that does not fall into this trap. I commend the authors for reporting this RCT and for their wisdom of being adequately cautious when formulating their conclusions.

I only wished it would happen more often!

There are dozens of observational studies of homeopathy which seem to suggest – at least to homeopaths – that homeopathic treatments generate health benefits. As these investigations lack a control group, their results can be all to easily invalidated by pointing out that factors like ‘regression towards the mean‘ (RTM, a statistical artefact caused by the phenomenon that a variable that is extreme on its first measurement tends to be closer to the average on its second measurement) might be the cause of the observed change. Thus the debate whether such observational data are reliable or not has been raging for decades. Now, German (pro-homeopathy) investigators have published a paper which potentially could resolve this dispute.

With this re-analysis of an observational study, the investigators wanted to evaluate whether the observed changes in previous cohort studies are due to RTM and to estimate RTM adjusted effects. SF-36 quality-of-life (QoL) data from a cohort of 2827 chronically diseased adults treated with homeopathy were reanalysed using a method described in 1991 by Mee and Chua’s. RTM adjusted effects, standardized by the respective standard deviation at baseline, were 0.12 (95% CI: 0.06-0.19, P < 0.001) in the mental and 0.25 (0.22-0.28, P < 0.001) in the physical summary score of the SF-36. Small-to-moderate effects were confirmed for most individual diagnoses in physical, but not in mental component scores. Under the assumption that the true population mean equals the mean of all actually diseased patients, RTM adjusted effects were confirmed for both scores in most diagnoses.

The authors reached the following conclusion: “In our paper we showed that the effects on quality of life observed in patients receiving homeopathic care in a usual care setting are small or moderate at maximum, but cannot be explained by RTM alone. Due to the uncontrolled study design they may, however, completely be due to nonspecific effects. All our analyses made a restrictive and conservative assumption, so the true treatment effects might be larger than shown.” 

Of course, the analysis heavily relies on the validity of Mee and Chua’s modified t-test. It requires the true mean in the target population to be known, a requirement that seldom can be fulfilled. The authors therefore took the SF-36 mean summary scores from the 1998 German health survey as proxies. I am not a statistician and therefore unable to tell how reliable this method might be (- if there is someone out there who can give us some guidance here, please post your comment).

In order to make sense of these data, we need to consider that, during the study period, about half of the patients admitted to have had additional visits to non-homeopathic doctors, and 27% also received conventional drugs. In addition, they would have benefitted from:

  • the benign history of the conditions they were suffering from,
  • a placebo-effect,
  • the care and attention they received
  • and all sorts of other non-specific effects.

So, considering these factors, what does this interesting re-analysis really tell us? My interpretation is as follows: the type of observational study that homeopaths are so fond of yields false-positive results. If we correct them – as the authors have done here for just one single factor, the RTM – the effect size gets significantly smaller. If we were able to correct them for some of the other factors mentioned above, the effect size would shrink more and more. And if we were able to correct them for all confounders, their results would almost certainly concur with those of rigorously controlled trials which demonstrate that homeopathic remedies are pure placebos.

I am quite sure that this interpretation is unpopular with homeopaths, but I am equally certain that it is correct.

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:

Mistletoe therapy

  • integrates with conventional cancer treatments
  • can be used for a wide range of cancers
  • may be started at any stage of the illness….

potential benefits…include:

  • 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.

Lymph oedema in the arms or legs is a frequent complication after lymph-node dissections for cancer. Treatment or prevention can be difficult, and the results  are often unsatisfactory. Consequently, the burden of suffering of cancer patients affected by this problem is immense.

Amongst several options, a little-known massage technique, called lymph-drainage (or lymphatic drainage, LD), is sometimes recommended. It consists of gentle manual movements which lightly push the lymph fluid through the lymphatic vessels that eventually enter into the blood circulation. During a session of lymph-drainage, a specially trained massage therapist lightly moves his or her hands along the lymph vessels to facilitate the lymph flow. The treatment is agreeable and relaxing, but does it really reduce the oedema?

A recent systematic review and meta-analysis of RCTs evaluated the effectiveness of LD in the prevention and treatment of breast-cancer related lymph-oedema. The primary outcome for prevention was the incidence of postoperative lymph-oedema. The outcome for management of  was a reduction in oedema volume.

In total, 10 RCTs with altogether 566 patients were identified. Two studies evaluating the preventive outcome of LD found no significant difference in the incidence of lymph-oedema between the LD and standard treatments. Seven studies assessed the reduction in arm volume, and found no significant difference between the LD and standard treatments.

The authors conclusion was negative about the value of LD: The current evidence from RCTs does not support the use of LD in preventing or treating lymph-oedema. However, clinical and statistical inconsistencies between the various studies confounded our evaluation of the effect of LD on breast-cancer-related lymph-oedema.

Perhaps a brand-new clinical trial which had not been included in the above assessment would have persuaded the authors to be a little more optimistic. This study evaluated the effectiveness of LD in the prevention of lymph-oedema after treatment of breast cancer. The study-population consisted of 67 women, who had undergone surgery for breast cancer. From the second day of surgery, 33 randomly chosen women were given LD. The control group consisted of 34 women who did not receive LD. Measurements of the volumes of both arms were taken before surgery and on days 2, 7, 14, and at 3 and 6 months after surgery.

Among the women who did not have LD, a significant increase in the arm volume on the operated side was observed after 6 month. There was no statistically significant  increase in the volume of the upper limb on the operated side in women who underwent LD.

The authors conclude that regardless of the surgery type and the number of the lymph nodes removed, LD effectively prevented lymph-oedema of the arm on the operated side. Even in high risk breast cancer treatments (operation plus irradiation), LD was demonstrated to be effective against arm volume increase. Even though confirmatory studies are needed, this study demonstrates that LD administered early after operation for breast cancer should be considered for the prevention of lymph-oedema.

So, does LD reduce oedema or not? This does not seem to be such a difficult question that it should take decades to resolve! And who would doubt that it is an important one? Lymph-oedema has the potential to seriously impede the quality of life of many patients, and it can even contribute to unnecessary mortality. The fact that the few available studies are too small and too weak to generate reliable results is disappointing and shines a dim light on the supposedly patient-centred research in oncology, in my view.

The concept of LD is plausible, at least some of the findings from clinical trials are encouraging, and the problem of lymph-oedema is both prevalent and relevant. So what is stopping us from funding a large, well-designed and definitive study?

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