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.