Pioneering clinic points to new directions in cancer treatment

By Jerome Burne

As anyone who is involved with cancer knows, you have two options. Follow the standard, scientifically validated route – variations on surgery, drugs and radiotherapy – supported by proper clinical trials or venture into the unapproved, unlicensed territory of complementary medicine frequently described as quackery. However there is a feature of mine in today’s Daily Mail that describes a ground-breaking third way.

It’s about the Care Oncology Clinic that’s recently opened up in Harley Street, where regular doctors are treating patients with a cocktail of four, old, off-patent drugs that consequently cost a paltry 200 to 400 pounds a year. The drugs haven’t been licenced to treat cancer but there is evidence that they can have a beneficial effect. Especially when combined.

They are being given on a well-established principle known as “off label prescribing”. In theory doctors can prescribe any drug for a condition, even though it’s not formally licenced to treat it, if they can show there is good scientific evidence to suggest it might help. As oncologists who works at the Care Oncology Clinic says: “Doctors prescribe off-label drugs every day.’ Except, until now, in the field of cancer.

Do read the feature if you have time as it fills in details that I’m not going to go into here. At the moment the clinic is intended for people with end-stage cancer who have pretty well run out of options. The idea of the cocktail, which includes such familiar drugs as statins and the diabetes drug metformin, is that it is taken along with any standard treatment.

Cancer treatment’s catch 22

The justification for their use, currently buried in the scientific literature, consists of evidence from cell research, animal studies and small trials that these and hundreds of other drugs have cancer killing abilities.

The clinic’s radical initiative highlights the catch 22 around cancer treatment that traps anyone who uses anything except surgery, licensed oncology drugs and radiation. (The original one, from a book of the same name, was that pilots could be taken off flying high-casualty-rate bombing missions in WWII on the grounds of insanity but asking for exemption on those grounds showed you were sane.)

The cancer drug version works like this. Treatment of cancer is firmly evidence-based, so for sake of patients’ safety and to keep out ineffective or fraudulent treatments, only drugs that have gone through the rigours of randomised controlled trials (RCTs) can be licensed for use. Sounds fair and reasonable.

However these trials cost tens of millions of pounds and the only organisations with the resources to run RCTs on them are the drug companies. But pharmaceutical companies are not, understandably, interested in trialling any treatments however promising – drugs or natural – that won’t be profitable. 

Bar for cancer drugs set very low

So although, in theory, any compound that can pass through the rigours of a randomised trial can be licensed to treat cancer, the catch 22 ensures that only drug company products make it through. The assumption here is that the trials do a good job at selecting the best safest and most effective drugs, however a recent editorial in the BMJ (‘Why do cancer drugs get such an easy ride?’) shows that the bar is set alarmingly low. 

See below for a summary of the key points. 

The clinic will be monitoring the effects of its cocktail and eventually reporting the results in a journal article. If the results show there are benefits from using these promising cheap drugs, the case for abandoning the catch 22 and running proper trials on them should become irresistible. In theory they could be done by charities such as the Wellcome Trust or the National Institute for Health Research, although so far they have shown little interest.

Another unconventional aspect of the clinic that could also lead to changes, is that the doctors there don’t dismiss any complementary and alternative treatments patients might be using as unproven and possibly dangerous. Instead they want to know what they are so they can offer advice and monitor the patients for side-effects or damaging interactions.

So far the clinic’s limited experience is that virtually all their patients have been using some form of additional non-drug treatment that they don’t tell their doctors about. Does this affect ongoing cancer drug trials? Almost certainly but since there is no data available it’s impossible to tell. Adopting the clinic’s more realistic approach could flag up risks and benefits.

Randomisation and blinding less likely

But just how scientifically rigorous are trials of cancer drugs anyway? Far less than they should be, according to the BMJ study by Donald Light, a professor of comparative health care and an economic and organizational sociologist at Rowan University School of Osteopathic Medicine in New Jersey.

His review shows that, despite the oncology community’s claim to occupy the scientific high ground, testing of cancer drugs is actually far less rigorous than the standard required for licencing in other fields. The basic principles of the RCT are that patients should be selected at random to get the drug or placebo and that neither doctors nor patients should know who is getting the drug or the placebo (double- blinded).

However a study that looked at nearly 9000 trials of cancer drugs, run between 2007 and 2010 found that compared with drugs for other conditions, they were  nearly 3 times more likely not to be randomised, 2.6 times more likely not to be compared with any other treatment and 1.8 times more likely not to be blinded.

Professor Light is a long term critic of the pharmaceutical industry. His latest book, The Risks of Prescription Drugs, which was commissioned by the Social Science Research Council, shows that side effects are a leading cause of accidents, hospitalization, and the 4th leading cause of death in the United States.

Tumour shrinkage an unreliable guide 

His review claims that the ‘easy ride from the regulators’ have resulted in cancer drugs that: ‘offer few significant benefits for patients.’ During the first ten years of its existence the European Medicines Agency (EMA) approved 71 drugs for the treatment of solid tumours. ‘Overall the new oncology drugs improved survival by a mean and median of 1.5 and 1.2 months respectively,’ he writes.

One reason for these unimpressive results could be the way that the trials assess whether a drug is having a beneficial effect. Usually it is done by measuring how much it shrinks the tumour. That was the basis on which most cancer drugs in Europe got a licence between 1995 and 2004. ‘However tumour shrinkage,’ Light writes ‘did not, most of the time, translate into significant survival benefit.’ 

What all this suggests is far from having a system that distinguishes between scientific and unscientific treatment we have one that is not operating in patient’s best interests. Trials need to be run with proper scientific rigour and there needs to be system testing promising treatments – regardless of their profit potential. The new clinic is a valuable step in that direction. 

Jerome Burne

Jerome Burne

Jerome Burne is the editor of HealthInsightUK. He is an award-winning journalist who has been specialising in medicine and health for the last 10 years and now works mainly for the Daily Mail. His most recent book “10 Secrets of Healthy Ageing” was written with nutritionist Patrick Holford. He blogs at “Body of Evidence” – jeromeburne.com. 2015: Finalist for 'Blogger of the Year' award from Medical Journalists' Association.

9 Comments

  • What a shame your insightful article was accompanied by another re-hash of conventional wisdom, much of it groundless, in the form of the World Cancer Research video!

    Looking at the “Tips”:

    1) Maintain a healthy weight
    This is probably confusing cause and effect. Excessive carbohydrate consumption causes weight gain, cardiovascular problems, Type II diabetes, and favours cancer growth. But until we get away from thinking that it’s the weight gain that causes the cancer, this idea os not going to help at all. Groundless.

    2) Move more (be active for at least 30 minutes every day)
    Nobody could argue with this, and there is solid sense in it… exercise will tend to cut down blood sugar surges, both by burning up carbohydrate (via muscle glycogen) and by increasing muscle capacity to absorb glucose in the form of glycogen. Sensible

    3) Eat more veg, fruit, whole grains & pulses
    A confusing mishmash! More veg (especially green leafy vegetables) will improve vitamin and mineral status, especially when combined with healthy fats such as butter to aid absorption. More fruit? Recipe for increasing blood sugar levels, favouring cancer growth. More whole grains? Idem. More pulses? I haven’t found any convincing evidence that pulses slow cancer growth, and again, their carb content probably won’t help. Groundless.

    4) Limit sugar and fat
    Another curate’s egg! Limit sugar? Great idea. In fact, cut it out, as it will provide tumours with all the glucose they need to grow and metastasise. Limit fat? Eating fat does not make people fat. And eating most calories as fat will help attain a state of nutritional ketosis, which is more and more proving to be the best strategy to cure cancer. Groundless.

    5) Limit red meat; avoid processed meat
    This is based on poorly-conducted epidemiology, which has been sunk with surgical precision by many real experts, such as Dr Malcolm Kendrick and Zoë Harcombe. The link between red meat and cancer is statistically insignificant. Studies linking “processed meat” to cancer invariably include such “processed meats” as hamburgers (with BUN), hot dogs (with BREAD), PASTA (with meat sauces) and PIZZA (with meat toppings). Remove the blood-sugar-boosting carbohydrates from that little lot and the observed link vanishes. Groundless.

    6) Cut down on alcohol
    There are no randomised controlled trials in this field, only vague case-controlled studies. It might make some sense in some cancers, though in others it probably doesn’t, as alcohol will kill off weaker cells (nod to jokes about Darwinian brain cell survival). Dubious

    7) Eat less salt
    What kind of dogmatic nonsense is this? Low salt consumption has been linked to poorer all-cause mortality, not better! Again, not a single controlled study has been done. Groundless.

    8) For cancer prevention, don’t use supplements
    A blanket recommendation indeed! Which supplements? Some may be linked to poorer survival, though there isn’t much in the literature, while others such as magnesium and Vitamin D, have been shown in real clinical studies to help overcome cancer. Far too vague to be of any use.

    9) If you can, breastfeed your baby
    Sensible; breastfeeding has a negative association with breast cancer, and this has been shown over many years.

    10) Cancer survivors (after treatment, cancer survivors should follow the Cancer Prevention Recommendations)
    In other words, “keep taking the tablets”. No matter how you overcame your cancer, do what we tell you!
    As a cancer survivor, I shall not be paying the slightest heed to any of the nonsense in this video.

    Sorry for the digression, Jerome! The Care Oncology Clinic sounds like an excellent initiative, and I wish it every success!

    • Editorial

      World cancer video came as a complete surprise to me too and agree that it is mostly either banal or not useful

  • It is interesting that you say statins are part of the cocktail of drugs that are being tested for anti-cancer activity. Dr Kendrick’s take on the idea that statins can prevent/treat cancer, is that those with high cholesterol are statistically less likely to get cancer, but more likely to be treated with statins – so that an observational study shows a negative correlation between statin use and cancer.

    Having experienced the side effects of Simvastatin, I suppose I am cautious about anything that helps to encourage the idea that statins are health-giving – though of course, if there is real evidence that they can be useful, they should be tried.

    • Editorial

      Yes I’ve read Dr Kendrick’s account and I can see the logic of suggesting that cutting the amount of cholesterol available to the brain when it makes up part of the wall of every neuron might well be harmful. However I was impressed by the care with which the team behind the clinic had done their research and I was persuaded that there is evidence for benefit. I’m going to ask Gregory Stoloff, the clinic’s director, to explain why he thinks Dr Kendrick is wrong; he will then, of course have the right to reply.

      • I am not sure you are referring to the post I am thinking of, in which Dr Kendrick puts forward the argument that there is a spurious correlation between statin use and less cancer:

        http://drmalcolmkendrick.org/2015/06/03/statins-and-cancer/

        In a nutshell, people with naturally high cholesterol get less cancer, but also get prescribed statins – so you end up with a spurious correlation between use of statins and less cancer!

        • Editorial

          That is indeed the post I am thinking of and it sounds like a good point. But the clinic is not using statins because it is in the pay of big pharma nor because those who have been doing the research are unable to distinguish cause from correlation. Malcolm’ post is concerned with statin use on its own, the clinic makes the point that the benefit arises from combining statins with several other drugs. especially the diabetes drug metformin. The two other drugs in the cocktail the clinic uses – an antibiotic and a de-worming pill – add to the effect. Also interesting, as I mention in the article, is that all the drugs impact on the metabolic pathways involved in generating energy in cancer cells. These are different to those at work when healthy cells make energy. For more detail on this see some of the articles under the “categories/cancer” section on this site. I’m hoping that the clinic’s director will make the case here in more detail.

  • Ah – so this is an attempt to exploit the fact that cancer cells usually depend on glycolysis for energy – which does sound exciting. Will it be also possible to test 3-bromopyruvate (as you discussed previously)?

    • Editorial

      As I understand it, there was no particular intention to target metabolic pathways.

      The 4 old drugs that were finally selected for inclusion in the cocktail were the “winners” from a list of around 5000 compounds that emerged from the company search as having cancer killing properties. They were selected following a number of criteria such as best level of evidence, having all been used together with no evidence of harmful interactions, good data on dosing etc etc.

      It then so happened that they all target various aspects of the glycolysis pathway. My hugely simplified account of what they do, which wasn’t published, was this:

      Statins: The drugs’ effect of blocking cholesterol production in the liver means that less is available to cancer cells (among others. This adversely affects cancer cells because a growing cancer is building new walls at a rapid rate, so removing building materials acts as a break on cancer’s growth. It also reduces the number of glucose receptors on the cell’s surface.

      Metformin – a clue that metformin might be effective against cancer came from research that showed that having diabetes raises your risk for cancer unless you have also been taking metformin. It also reduces amount of glucose available because makes insulin more effective at clearing it away and it blocks one of the processes the cancer cells use to make energy

      Doxycycline (tetracycline antibiotic) – increases the effect of some of the regular cancer drugs, blocks several of the many (27) steps needed to turn glucose into energy (known as glycolysis), and kills bacteria found in some cancer cells that help to damp down the immune system. Some bacteria are able to reduce immune system activity for its own protection, an ability which cancer cells also have,

      Mebendazole (worming drug) Blocks some more of the steps in turning sugar into energy. The overlapping effects of these drugs explains why they can be more effective when given as a cocktail.

      As far as I know the drug that looked promising according to Travis’s book -3-bromopyruvate – is still on the back-burner.

  • Thanks for supplying all those extra details – I do hope this is an amazing success!

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