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.
“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.
A viral immunotherapy success story
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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