“This film charts the remarkable story of Ben Williams, professor emeritus of experimental psychology at University of California, San Diego. Diagnosed in 1995 with a lethal cancer, a primary brain tumour called glioblastoma multiforme, he was given just a few months to live.
But a natural born maverick, and rigorous scientist, Ben decided he would not go down without a fight. Nineteen years later his story is an inspiration to patients the world over, whilst his case is dismissed by the medical community as just one of a handful of statistical outliers.”
Even today the average life expectancy for patients with glioblastoma multiforme is just 15 months, with survival rates highest among young people. Fewer than 10 per cent of people aged 50 and above survive for five years. So it is against all odds that Professor Williams has just celebrated his 70th birthday and 20 years of clean MRI scans.
“I’d been told that my chemotherapy wouldn’t get rid of the tumour completely or indefinitely, so I focused on finding agents that might make chemo work better for me,” he says. Sure enough, after his fourth round of chemotherapy in 1996, Prof Williams’s tumour had vanished. It has never returned and thousands of people, including oncologists, have sought his advice since on ”beating” a cancer known in medical circles as “The Terminator”.
In mainstream oncology Professor Williams is considered a freak case and his strategy of fighting cancer “using every potentially efficacious agent I could lay my hands on” attracts suspicion. Yet a growing number of specialists and researchers say there is evidence that some of the common pills taken daily by millions for other ailments, could be ‘‘repurposed’’ to help in the battle against cancer.
“We just need to look in our medicine cabinets,” says Pan Pantziarka, scientist and UK spokesman for the Anticancer Fund, a Belgian non-profit organisation run by researchers and doctors. “There is strong evidence that some of the medicines we use every day have anti-cancer properties.”
At present, the pharmaceutical industry is using advances in our understanding of genetics to create so-called ‘‘magic bullets’’, a new generation of ever smarter, ever more targeted therapies. These act like snipers, interfering with specific cell proteins or signalling pathways that have a role in cancer. Major successes with this approach include the chronic myeloid leukaemia drug imatinib (Glivec) which blocks a protein that makes cancer cells grow and divide.
But, according to Professor Angus Dalgleish, Foundation Chair in Oncology at St George’s Hospital, University of London, many targeted therapies are eventually doomed to failure.
“Cancer will do everything it can to survive and avoid being hit,” he says. “It’s like a traveller who wants to cross London on the Tube. Yes, you could block him by taking out a major station like Oxford Circus, but he’ll just switch to a different line. It’s the same with cancer. After getting hammered by one agent, the tumour quickly reinvents itself through evolution. I always delay giving these targeted therapies as long as possible because I know they’re not going to be working a few months down the line.”
It costs more than $1billion (£650 million) to bring a new cancer drug to market and takes more than a decade. As drug companies face an increasingly uphill battle to invent new chemical entities that can be patented, they pass on the cost of a 90 per cent-plus failure rate, expensive trials and marketing to the NHS, insurance companies, healthcare providers and patients. Such is the spiralling cost that the Government now runs a separate £280 million-a-year Cancer Drugs Fund to shield NHS budgets – and even that is expected to overspend by £100 million this year. In January, the Government announced that 16 life-extending drugs would no longer be paid for by the Fund because of cost-cutting.
The good news is that early-stage laboratory experiments and clinical studies, as well as large scale epidemiological research point to the potential cancer-fighting properties of dozens of existing medicines that millions of people take safely every day for other ailments. Aspirin is the most high-profile example. Research funded in part by Cancer Research UK shows that it can significantly cut the risk of bowel, throat and stomach cancer if taken daily by people aged 50-65 (although the CRC warns on its website that aspirin can have side effects and should not be taken regularly without medical advice).
The Repurposing Drugs in Oncology (ReDo) Project, an international collaboration between the Anticancer Fund and US-based non-profit organisation Global Cures has identified 70 potential agents for which there is evidence of cancer-fighting properties. These include the diabetes tablet metformin, cholesterol-lowering statins, the antacid cimetidine, the de-worming tablet mebendazole, the anti-fungal itraconazole, and all the drugs Professor Williams took as he battled his brain tumour.
“Most modern cancer drugs are known as targeted therapies because they are aimed at very specific targets inside cancer cells,” says Dr Pantziarka. “But these older medicines are known as ‘dirty drugs’ because they have multiple targets, interfering with more than one protein or signalling pathway at a time. Used in combination, they could be very effective.
“If these medicines were coming out today, some would be blockbuster cancer drugs. But most are no longer covered by patents so the pharmaceutical industry has no financial incentive to investigate them.”
Even though these medicines are not officially labelled as cancer drugs, doctors are legally entitled to prescribe them “off-label” if there are solid grounds to believe they will be beneficial. Indeed, Lord Saatchi’s Medical Innovation Bill, which is supported by the Telegraph, aims to give oncologists (and specialists in other fields) more confidence to be experimental in treating terminally ill patients for whom all existing therapies have failed and who are prepared to take risks. But in practice, most oncologists are unwilling to prescribe drugs that have not passed final-stage (Phase III) clinical trials for a particular type of cancer, and even more wary of combinations that may interfere with conventional treatment or have unforeseen side effects.
Professor Dalgleish is one of the few UK doctors willing to think differently. “Say we have a patient who is fit and healthy in many ways but is going to be dead within months. If that patient asks me, ‘Is there anything else I can do?’ I will say, ‘Yes. The data suggests you could consider metformin which appears to selectively reduce glucose uptake by tumour cells as opposed to normal cells. I suggest aspirin to tackle your inflammation and let’s correct your vitamin D levels to boost your immune system.’
“I call it creative compassion because it’s not in the rule book and it’s what I would want for myself if I were in the same position. I wouldn’t want to just be told to go and see the palliative care person.”
Professor Justin Stebbing, of Imperial College London, the oncologist who treated actress Lynda Bellingham before her death from bowel cancer last year, agrees with the approach, though he tends not to prescribe off-label drugs himself.
“That’s not because I’m ethically opposed to the idea, but it’s not something I do every day so I’m not knowledgeable about dosages,” he says. “However, I don’t have a problem if patients get the drugs elsewhere and am open to referring them to trials that test these alternative approaches.
“As a profession, we can be cruel to cancer patients, giving them treatments that are horribly toxic with minimal benefits. I find it very frustrating when my colleagues are dismissive of patients who want to try other things that are non-toxic and may extend their lives.”
Professors Dalgleish and Stebbing are the co-authors of a study into “cocktail cancer therapy” currently taking place at the Care Oncology Clinic in London. Over the next five years, the private clinic run by biotech firm SEEK is aiming to treat more than 10,000 cancer patients with a combination of four ‘dirty drugs’ — statins, metformin, the de-worming drug mebendazole and doxycycline, a common antibiotic.
Gregory Stoloff, founder of SEEK, says it’s a non-profit trial funded by patients themselves, who pay £400 for the initial consultation, then £200 every three months to cover the cost of the drugs, consultations and the trial.
“Oncologists refer patients to us who have run out of treatment options and we put all of them on the treatment right away,” he says. Because nobody is given a placebo, this is not a controlled clinical trial. But SEEK hopes that treating thousands of people will create enough data to enable an effective comparison with cancer survival rates in the rest of the population. “Controlled clinical trials are all very well but when you have people who are expected to die within months they want treatment now. And these are very safe medicines that people have been taking for decades.”
Although Phase III clinical trials remain the gold standard for science, they don’t necessarily serve cancer patients well, says US campaignerDominic Hill, in whose film Prof Williams appears, along with oncologists researchers and other cancer survivors.
“Today’s lifesaving treatment for HIV [called antiretrovirals] is given to patients despite it never having passed a randomised Phase III clinical trial,” Mr Hill, whose brother-in-law Andreas died of a brain tumour in 2010, points out.
“How many cancer patients must die before the regulators recognise that this approach needs to be adapted to oncology?”
Dominic Hill’s film Surviving Terminal Cancer is free to watch onsurvivingterminalcancer.com
The Drugs in Question: the evidence for and against
Metformin: Several studies suggest that tumours grow more slowly in cancer patients who take this anti-diabetic drug. Early-stage clinical trials are investigating its potential to prevent various cancers including prostate, breast, colorectal and endometrial.
Statins: Preclinical studies suggest these cholesterol-lowering heart drugs may prevent various cancers and stop them spreading. One recent meta-analysis associated a daily statin with a significant risk reduction of liver cancer.
Mebendazole: There is evidence this drug – usually prescribed to treat parasitical worm infections — may inhibit cancer cell growth and secondary tumours, though no clinical trials have been completed.
Cimetidine: This over-the-counter antacid has direct anti-proliferative effects on cancer cells, inhibits cell adhesion, reduces tumour angiogenesis (growth of blood vessels essential to a developing tumour) and also boosts anti-cancer immunity in various cancers.
Itraconazole: The common anti-fungal treatment is also thought to be anti-angiogenic and has shown promise as an agent for prostate cancer, non-small cell lung cancer and basal cell carcinoma, the most common kind of skin cancer.
Isotretinoin: This acne drug, marketed as Accutane, is occasionally used to treat certain skin cancers and neurological cancers as well as to prevent the recurrence of some brain tumours, although some studies suggest it is ineffective.
What does Cancer Research UK think?
Professor Peter Johnson, chief clinician at Cancer Research UK, said: ‘It’s completely understandable that when faced with a terminal cancer, patients and their doctors want to explore every possible treatment option, but it’s important to balance the wish to do something against the problems such as side effects and false hopes.
“Cancer doctors in the UK are very innovative and often try new treatments if they and the patient feel this might be of benefit. The thing which sometimes prevents us from using different treatments is not our reluctance or a fear of being sued, but NHS funding. The NHS requires good evidence a treatment will work, which is why we carry out research trials, and more UK patients go on clinical trials than anywhere else in the world.
“Clinical trials are essential to find out whether new treatments are safe, if they are better than the standard care, and which patient groups will benefit. The only way to improve cancer medicine and show that a new treatment should be given to patients is by analysing trial results, which are scrutinised to make sure that they are ethically sound and scientifically valid. There are many different ways to do trials, but they all have the same goal: to find the best and safest forms of treatment. The people who take part in trials know that even if they themselves don’t benefit, they will help other people in the future.
“It doesn’t make sense for patients to withhold information from their doctor about other medicines they are taking. Many drugs, even those sold as natural remedies, can interfere with each other and the results can be very dangerous, or even fatal.”
Update on the Saatchi Bill
The Medical Innovation Bill, which would protect patients and doctors who want to try experimental treatments, is just days away from either becoming law — or becoming a footnote in the history of scientificadvance.The Private Member’s bill sponsored by Lord Saatchi has been debated four times in the House of Lords, tested and amended by Labour, Tory and Lib Dem peers and scrutinised and approved by doctors, lawyers and judges in the upper chamber. It is supported by both the Government and Opposition front benches. It is also backed by patients and their families – more than 40,000 have signed up as Medical Innovation Bill supporters.The Bill now includes a register that will see the results of all innovations recorded so they can be shared and used by other doctors and researchers. Having been amended and passed by the Lords, the Bill must now be approved by MPs in the Commons. But time is running out – Parliament has only weeks to complete its business before it is dissolved ahead of the May election. It is now up to the Government to find time for the Bill to be debated. If this does not happen the Bill will fall.