The professor who ‘cured’ his cancer with a cocktail of everyday pills and 20 years on remains disease-free

Ben Williams’ aggressive brain tumour was treated with conventional therapies – and with a mix of common drugs, including those for acne, insomnia and high blood pressure, as revealed in a new documentary. Could this approach work for others?

By Ruth Wood – 8:00AM GMT 23 Feb 2015

ONE day, some two decades ago, Ben Williams set out from his home in San Diego, California, to cross the border into Mexico in search of acne tablets. The 50-year-old psychology professor didn’t actually suffer from acne. What he had was the deadliest type of brain tumour, a glioblastoma multiforme that was the size of a large orange. A leading neuro-oncologist from Texas had suggested that a skin treatment, called Accutane, might help him.

Prof Ben Williams was diagnosed with the tumour in March 1995. “The entire right side of my brain was infested with a tumour,” he recalls. “Apparently brain tumours as large and ugly as mine are a notable event. Soon half the neurology department had shown up to look at the scans.” He underwent surgery the following afternoon. However, relations with his neurologist soon became strained due to his dogged insistence on researching his own treatments.

His doctor wanted him to stick to the standard regimen of surgery, radiotherapy and chemotherapy. But the rebellious Harvard alumnus insisted on adding to this a veritable cocktail of drugs – in addition to the acne pills, there were blood pressure and insomnia tablets. All were cheap and had little or no toxicity, and for all of them Williams had gathered some credible evidence from scientific trials that they might reduce his tumour, boost his immune system and make chemotherapy more effective. But none had been approved in the United States for use in the management of brain tumours, so his own specialist had dismissed them.

“He said I would drive myself crazy researching all these things and that I might hurt myself,” recalls Prof Williams, whose story is told in a new film, Surviving Terminal Cancer, released online today. “I almost laughed. Hurt myself? I had the most aggressive kind of brain tumour. I was expected to die in a year. What did I have to lose?”

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.

Ben Williams Remarkable Survival Story:

“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. 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.

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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.

Surviving Terminal Cancer teaser from Indigo Rebel on Vimeo.

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 campaigner Dominic 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 on survivingterminalcancer.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 scientific advance.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.

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A viral immunotherapy success story

The first viral immunotherapy was approved 10 years ago in China, a cold virus engineered to treat head and neck cancer. China became a mecca for those who couldn’t get the therapy in their home countries.

After years of U.S. research established the therapy was safe, the FDA became sold. Late last month, it approved the first U.S. viral immunotherapy, a herpes-based biologic to treat melanoma.

The benefits seem modest – in its last clinical trial, it shrank tumors in patients with advanced disease, though the survival figures stopped short of statistical significance, but researchers called it a huge milestone.

“This is going to float all boats,” said Dr. Stephen Russell, a professor of molecular medicine and viral immunotherapy researcher at the Mayo Clinic in Minnesota. “It’s a signal to pharmaceutical companies that such drugs can be approved.”

The treatment is known as oncolytic virotherapy, in which the virus infects and replicates inside cancer cells, causing them to burst. The eruption releases tumor proteins that prod the immune response.

Dr David Baskin’s work is a cousin of such therapy. Instead of killing the tumor, his genetically engineered virus acts as a Trojan horse.

Dr Baskin treated Futer's severe brain cancer with an oncolytic virus

Patient Story: Futer, a former mechanic who managed his family’s trust, first sought medical care on Christmas Eve 2006. He’d spent three days in bed, sure “something wasn’t right,” though all he really felt was a severe headache. By the time he got to a clinic near his Cypress home, he was vomiting profusely, a little blood mixed in. Staffers sent him to the emergency department of Methodist’s Willowbrook campus.

After immediate care and testing, Futer was filling out paperwork when a doctor told him it could wait. “That’s it,” he remembers the doctor saying. “Half your brain is cancer.” The left half harbored glioblastoma multiforme, the most common and most aggressive malignant primary brain tumor.

Half of people diagnosed with the tumor die within a year, 85 percent within three years. Even when a surgeon seems to have removed the entire tumor, cells remain seeded in the brain, inevitably giving birth to new tumors. Doctors compare the cancer to a weed that keeps sprouting tendrils. Willowbrook doctors sent Futer to Methodist’s flagship hospital in the Texas Medical Center, where neurosurgeon, Dr David Baskin was on call. One look at Futer’s scans told Baskin all he needed to know.

The news overwhelmed Futer, who’d been happily living day to day. He was calm, stoic, but Baskin could see the fear in his eyes.

Viral immunotherapy represented a long shot, but Baskin was excited to have something to offer Futer besides standard therapy, so unlikely to make any meaningful difference. Futer was all for it, not just on the chance it might help him, but for the more likely benefit it might provide future patients.

Ten days later, Baskin performed the surgery and injected the viral drug, called AdV-Tk. When he closed up Futer’s skull, he had no idea what to expect.

Dr Baskin, 63, had always been fascinated by the mind. He aspired to be, first, a psychologist, then a psychiatrist and finally a neurologist, each time finding the newly chosen specialty an upgrade over the old one.

He had no interest in surgery – “too bloody, gory” – but figured since he’d be referring patients to neurosurgeons, he should learn what they do. At a rotation soon after, an eminent neurosurgeon enlisted his assistance for a nine-hour operation removing a tumor from a patient’s spinal cord.

“The next day, the patient walked,” Baskin said. “I knew that’s what I wanted to do.”

Glioblastomas promise no such happy ending. Baskin describes the horrific moment when a patient, unaware what’s ahead, looks at him and says, “What do you think, doctor?” and the answer, however delicately put, is that his disease is usually a death sentence. 

How a new, minimally invasive treatment, uses oncolytic viruses to attack and kill brain cancer cells

Background: Many of the first researchers working with oncolytic viruses weren’t counting on an immune response. They just saw a virus’s potential as a killing machine.

At M.D. Anderson, for instance, the husband-wife team of Juan Fueyo and Candelaria Gomez-Manzano 15 years ago engineered a cold virus that targets proteins that exist only in cancer. Injected into brain tumors through a hole in the skull, the virus enters malignant cells and begins making copies of itself until the cells explode, which propels viral particles forward in a wave-like motion that infects other cancer cells.

Those experiments were in mice lacking immune systems. Only in a recently completed early-stage clinical trial did Lang’s team confirm the therapy also generates a response from the immune system, which, tricked into thinking the patient is suffering from the common cold, mounts an attack on the virus. Cancer cells get caught in the crossfire.

Baskin’s work always aimed to enlist the immune system. It dates to laboratory work, initially focused on prostate cancer, conducted at Baylor College of Medicine in the late 1990s. Intrigued by presentations of the research, Baskin determined to apply it to brain cancer, where there had been little progress over the decades.

In Baskin’s research program, a non-replicating, gutted cold virus is used strategically – like the ancient Trojans with their wooden horse – to carry a piece of herpes DNA into tumor cells. The virus doesn’t attack by itself, but following the injections, patients are given Valtrex, the oral medication used to treat herpes. When the drug attacks the herpes DNA, it creates a new protein that blasts the cancer cells, making them self-destruct and release other proteins that initiate an immune response.

What type of oncolytic viruses are used?

Cold and herpes viruses are the most common infections being used as immunotherapies against cancer, but researchers are experimenting with measles, mumps, polio, viruses that cause diarrhea and respiratory problems, viruses that afflict cattle and birds. A handful of researchers are working with bacteria, such as listeria and salmonella. In all, more than 60 clinical oncolytic virotherapy trials are ongoing in the U.S., according to the Cancer Research Institute, a 62-year-old immunotherapy advocacy group. The trials involve cancers from breast and ovarian to prostate and pancreatic.

“It’s impossible to know what’s the best agent at this point, but I think the best perspective is the more options we have, the better,” said M.D. Anderson’s Lang. “Different tumors might respond best to different viral immunotherapies.” 

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Experts caution that the research is effective in at best a fraction of patients and much in need of randomized trials to provide hard evidence of real benefits. Russell estimated the field is at the equivalent of mile 5 in a marathon.

Big questions remain. Do the injections work better if given before surgery so there’s ample tumor tissue for the virus to grow in? Can the immune system be controlled so it doesn’t kill the virus before it can proliferate through cancer cells and have its desired effect?

One big hope involves combining viral efforts with checkpoint blockade therapy, an approach pioneered by Houston scientist Jim Allison.

Allison identified a natural brake that reins in the body’s defense, then developed a drug that removes the brake and unleashes the immune system to attack cancer. A network of such brakes was subsequently discovered, and scientists around the world are now investigating the best ones to target different cancers, often in combination with other therapies.

Researchers at Advantagene Inc., AdV-Tk’s manufacturer, have combined the two therapies in mice and found they worked better than the viral biologic alone. Merck recently announced plans to launch an intermediate-stage trial pairing a checkpoint blockade drug with M.D. Anderson’s oncolytic virotherapy.

The furthest along of the viral immunotherapies may belong to Baskin, who expects Advantagene to launch a late-stage, randomized trial of AdV-Tk in early 2016. At a major cancer conference in June, Baskin reported that 32 percent of patients who got AdV-Tk plus standard treatment in the trial that enrolled Futer survived at least three years after diagnosis, compared to 6 percent of patients who concurrently got identical treatment minus the AdV-Tk. Three of the trial’s 48 patients are still alive, all more than five years out.

From the beginning, Futer had an agreement with Baskin: that he always be honest with him. If his chances of living more than a year were just 20 percent, Baskin shouldn’t shade the truth. Baskin hadn’t – that was the prognosis he originally gave Futer.

Studying Futer’s scans before his three- and six-month follow-ups, Baskin fretted. Futer’s tumor appeared bigger than it had been before surgery. “I don’t know about this,” Baskin told Futer at the second appointment. “This looks bad.”

Still, Baskin figured any patient with a tumor that big would be horribly impaired. Futer was doing fine – so fine he was able that summer to persuade Baskin to let him fly to England, where he was born and lived for eight years, so he could assist an old friend participating in a sheepdog trial. Baskin thought Futer’s lack of symptoms suggested things might not be as they seemed.

They weren’t. At one year, scans showed Futer’s tumor had shrunk by a third. At two years, it was down to half its original size, and at three, just 25 percent remained. In ensuing years, the tumor melted away, culminating last month, at Futer’s first appointment with Baskin in a year, when a last sliver seen on the 2014 scan was gone. Baskin had never before had a glioblastoma patient still alive nearly nine years after diagnosis.

What initially appeared to be tumor growth was actually inflammation caused by the immune system’s attack on Futer’s cancer, now a known hallmark of immunotherapy. The medical term is “pseudo-progression,” which often precedes a positive, prolonged response to therapy.

The cancer left Futer with short-term memory issues, and he is on disability. Since his initial diagnosis, he’s become extroverted and temperamental. Where he formerly had the disposition of a St. Bernard, according to his dad, he now occasionally brings to mind a German shepherd.

Futer’s recovery has been an “emotional boost for everyone,” Baskin said. “If I wasn’t a scientist,” he said, “I’d call this a miracle – and maybe it is.” At last month’s appointment, Baskin and Futer looked at scans, from pre-surgery to now. Baskin floated the idea of having an immunologist analyze Futer’s blood in hopes of finding clues that might suggest why he responded so well. He told of tweets doctors sent after a lecture that highlighted Futer’s case.

“You’re helping more people than you know,” Baskin said. “I’m having a hard time not crying,” said Futer, head lowered, voice breaking. The battle is likely not over. This spring, Futer was diagnosed with kidney cancer, unrelated to his brain tumor. A surgical team removed the mass, and for now, he is cancer-free.

     

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