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Is the war on cancer an ‘utter failure’?: A sobering look at how billions in research money is spent

The side effects John-Peter Bradford endured four years ago as he underwent radiation therapy and surgery for throat cancer were, he says, “barbaric.” Still, the potent treatment worked, eradicating the tumour and saving his life.

As his family confronts the shock of another, more advanced malignancy today, however, the Ottawa management consultant is agonizingly aware that many cancers remain incurable, despite 40 years of hugely expensive research into the disease and how to treat it.

“This thing called a war on cancer … has been an utter failure with metastatic cancers,” estimates Mr. Bradford, 70, author of a book about his own experiences as a patient. “We have to try different things, and we have to try them differently.”

His sobering view is not exactly embraced by the disease’s most public face: cancer charities and hospitals, which still confidently promise to “outrun cancer,” while exhorting donors to walk, cycle or even play road hockey “for the cure.”

Yet some scientists believe the quest for an antidote to the world’s number-one health risk is indeed being lost, even as research costs surge well past $100-billion.

Though the per-capita cancer mortality has fallen, the total number of deaths continues to soar, as the rate of new cases also climbs. Jim Watson, the Nobel-winning discoverer of DNA’s double-helix structure, caused a minor sensation recently by arguing that curing most metastatic cancers — cancers that spread in the body — remains more daunting than ever, while researchers pursue scientific dead ends.

Lamenting a “conservative” research establishment that he suggested is reluctant to take scientific risks, he urged scientists to follow new, unexplored, yet more promising directions.
Of all the much-hyped and pricey new cancer drugs entering the market — the most tangible results of so much research — a few have worked wonders, but the benefits in many cases are minimal, some doctors complain, with serious side effects downplayed.

“It’s been a very, very chaotic process of looking for cancer cures, and it’s not been tremendously successful,” said Jack Siemiatycki, a prominent cancer epidemiologist at the University of Montreal, who suggested that there is little co-ordination among the myriad cancer labs and clinics. “There have been successes, but it’s a modest success story.”

Michael Pollak, an oncologist and internationally recognized treatment researcher across town at McGill University, maintains that cancer science has, in fact, made great strides in the last 40 years. But even he admits that well-meaning scientists often leave patients with an exaggerated sense of their achievements.

“The researchers are always announcing fantastic progress and breakthroughs — and the patients are still getting sick and dying,” said Dr. Pollak. “The people who are announcing cancer breakthroughs, I’d like them to walk through the cancer ward. … You see all these thin and kind of desperate patients.”

The “spectacular” volume of knowledge accumulated about the disease is one of science’s great accomplishments, said Dr. Ian Tannock, an oncologist and researcher at Toronto’s Princess Margaret Hospital. Asked about his cancer centre’s own slogan “conquer cancer in our lifetime,” though, Dr. Tannock is more cautious. He said he doesn’t believe that widespread cures will come in his or his children’s time on earth, foreseeing a series of small advances, but no dramatic breakthroughs.

The results of modern cancer research are typically measured from the date in 1971 when Richard Nixon, then U.S. president, launched what was dubbed the war on cancer, with many likening it at the time to America’s triumphant drive to put a man on the moon. And the massive dollars assigned by the U.S. since have been mirrored on a smaller scale in other countries, including Canada.

Yet that era’s great expectations were hopelessly naive, argues Dr. Benjamin Neel, head of the Ontario Cancer Institute and an American whose medical training began in the same era.

Launching a war on cancer in 1971 “would be sort of like Kennedy trying to put a man on the moon in the 1600s,” he said. “We had no fundamental understanding of the disease.”

Since then, though, scientists have managed to draw a detailed map of how cancer works, identifying genetic anomalies that allow cells to multiply uncontrollably and resist the natural death that comes to normal cells. Dr. Neel calls it a springboard of knowledge that should lead to something closer to cures for even the most stubborn cases, sometime down the road.

“I don’t think there has been a single better, more efficient expenditure of public money,” he said of the research into the science behind cancer. “Far from being embarrassed, we should be trumpeting those successes.”

In the U.S. alone, the National Cancer Institute (NCI) — created by the Nixon administration more than 40 years ago to help fight the war — has doled out close to $100-billion in funding, with hundreds of millions more raised and spent by cancer charities and hospital foundations.

The numbers in Canada are smaller, even when put on a per-capita basis, but still impressive. Total cancer-research spending here in 2009 was $545-million, according to the Canadian Cancer Research Alliance, with the biggest chunk ($132-million) coming from the Canadian Institutes of Health Research, this country’s counterpart to the NCI. More than 60% of the cancer money goes to work on biology and treatments. By comparison, a recent study put total spending on research into cardiovascular disease — Canada’s next-biggest killer — at under $100-million, a fifth as much.

Despite definite patches of hope, though, the statistics remain grim, with an estimated 186,000 Canadians newly diagnosed with the disease in 2012 and 75,000 deaths. Even after the effect of an ageing population is filtered out, data show the rate of new cases per capita has been rising, albeit slightly, now at 456 cancer patients per 100,000 people.

While the overall number of deaths is 50% higher than two decades ago, the good news is that the mortality rate per capita — again after removing the effects of a greying population — has dropped to 184 per 100,000, from 243.

But here’s the catch: Much of that reduced lethality, is due primarily to one thing, and it has nothing to do with medical breakthroughs but, rather, the precipitous drop in the smoking rate that prevented legions of people from even getting sick with cancer in the first place.

“I think the most important cancer research of the 20th century by far was the discovery of the smoking association,” said Dr. Siemiatycki. “It wiped out one-third of cancer.”

An American Cancer Society study last year suggested that overall cancer mortality would barely have shrunk at all after the early 1990s if not for the huge societal shift away from tobacco.


For some patients struck with certain cancers, it’s true that the prognosis is decidedly better now than four decades ago. Childhood leukemia, a virtual death sentence in the 1960s, now has an 80% survival rate; Hodgkin’s disease is all but curable, while some of the major adult cancers, like breast and prostate, can be successfully treated now, if caught early enough.

Still, many advances have come through better screening programs — improved mammography for breast cancer that can detect a tumour while it’s still small — and better use of the same tried and true treatments of surgery, radiation and chemotherapy, with the latter two attacking cancerous and healthy cells almost indiscriminately.

“We still tend to treat cancer today with, in some cases, many of the same tools we used 40 years ago,” said Sian Bevan, research director of the Canadian Cancer Society.

Those traditional treatments, honed over the decades to reduce the damage to normal tissue, were what saved Mr. Bradford. Yet they still come at a heavy cost. He lost his sense of taste and can no longer create saliva. Much of his throat was removed.

In a recent book lamenting the limited progress against cancer, Margaret Cuomo, a New York radiologist, also notes that radiation can actually cause more malignancy later in life, citing the case of Robin Roberts, the Good Morning America host, whose 2012 public bout with cancer may have been triggered by treatment for a breast tumour five years earlier.

The drive in drug development now is to narrowly target the genetic mutations that give cancer cells their deadly characteristics, ideally avoiding widespread harm to healthy cells. There are certainly some success stories.

For the one-fifth of breast-cancer patients who have the HER2 protein, the drug Herceptin, in combination with surgery and chemotherapy, has helped make the disease virtually curable when found early enough, said Dr. Tannock.

Gleevac, another targeted drug, has “completely transformed” chronic myelogenous leukemia from a certain death sentence to usually survivable, said Christine Williams, research vice- president at the Canadian Cancer Society.

Bruce Dickinson of St. Catharines, Ont., who suffers from myelofibrosis, a rare blood cancer, credits the fact he is still alive today to the new drug Jakavi, which has stabilized his fast-deteriorating health. But the 60-year-old relies on manufacturer Novartis to provide it free, on a humanitarian basis, since the $7,500 monthly price is almost four times the income he and his wife receive from disability benefits.

The agency that assesses oncology medications for the provinces, recently recommended the drug be covered under government plans, but only if the price was cut to make it more cost-effective, noting that Jakavi’s ability to extend life remains uncertain.

Along with such breakthroughs, meanwhile, have come a slew of new, targeted treatments with less glorious results. Many are approved based on extending patients’ lives by just weeks beyond existing treatment courses, or not at all, and, as Dr. Tannock and colleagues have shown in a series of recent studies, they often feature serious side effects that come to light well after hitting the market.

And their price tags are typically sky high. A group of oncologists at New York’s Sloan-Kettering Cancer Center recently refused to prescribe Zaltrap for late-stage colorectal cancer, noting in a New York Times op-ed piece that its $11,000 monthly cost was twice that of an older drug, Avastin. Yet both had the same, modest effect, extending survival by 1.4 months on average.

But even Avastin itself is “a great disappointment” in treating cancer, in Dr. Tannock’s estimation, despite being the world’s ninth-highest-selling drug in 2012, raking in $6-billion in sales, bolstered by extensive, mostly positive media coverage.

Those extra few weeks or months afforded by new drugs, while seeming insignificant from a distance, can be important to patients, stressed Dr. Bevan at the Cancer Society. On the other hand, some are surprised by the modest benefits after hearing of great breakthroughs, said Dr. Pollack.
“If you’re a patient, six months is appreciated, but it’s not exactly what they had in mind,” he said. “They want a cure.”


Of course, trying to defeat cancer at the molecular level is a challenge like few others in medical science, despite a history of laboratory discoveries — from Frederick Banting’s insulin to Fleming’s penicillin — that were able to vastly transform the treatment of other illnesses.

It has turned out, for starters, that cancer is actually as many as 300 different diseases, with qualities that make them uniquely difficult to eradicate. Disease-causing bacteria, by contrast, are foreign invaders whose biology is sufficiently different from normal human cells that it is possible to kill them without harming the patient, noted Dr. Pollak. Cancer cells — a case of the body’s own internal biology gone awry — are so similar to normal cells, that most of the weapons that obliterate them also endanger healthy tissue, he said.

Plus, cancer patients have as many as 100 million cancerous cells, and each one must be dispatched to prevent the disease roaring back, much like a few neglected weeds multiplying on a front lawn. “The prize [in oncology] for almost succeeding is not that large,” said Dr. Pollak.

The challenge has proven all but insurmountable when cancer spreads beyond its initial site, Dr. Watson points out in his recent article in the journal Open Biology.

Once metastasized, the major adult cancers remain incurable; the new, targeted drugs “only temporarily hold back the fatal ravages” of lung, colon and breast tumours that have spread, he wrote.
He advocates shifting money away from developing therapies designed to stop genetic triggers for specific cancers, and toward uncovering ones that attack features common to various malignancies. Potential targets include a protein called Myc, which he said may be an essential feature in many incurable cancers.

He complained, though, that researchers, rather than trying to “aim big,” are assaulting the disease on a “never-frantic, largely five-day working week.” The biggest obstacle to progress, Dr. Watson added, is “inherently conservative research establishments” averse to experimenting with innovative ideas.
Dr. Pollak recounted how Dr. Watson, the field’s elder statesman, visited him recently in Montreal and essentially argued for inventive research that, while quite likely to fail, has a shot at producing truly transformative results.

The McGill professor said he agreed there should be more of that kind of high-risk, high-yield science in the mix. Funding bodies meting out limited dollars tend to discourage scientific gambles, though, rewarding those who propose building incrementally on previous findings, rather than bolting off in new directions, he said.

The competition between labs to achieve some sought-after goal first, while healthy in many respects, also risks leading to duplication of effort and secrecy that may not aid the greater good, said Dr. Pollak.

Dr. Neel said Dr. Watson is right that individual targeted cancer therapies will have limited impact on their own, but predicted the future of treatment will involve using several types of drugs that attack different aspects of a cancer, much as chemotherapy is employed now.

And Dr. Watson does not have an entirely spotless record as a scientific prophet. He predicted in 1998 that new drugs that curbed blood flow to tumours would result in a cancer cure within two years; once tested on humans, the medications had only minor benefits.

But if science is making only tentative steps toward overcoming cancer’s worst cases, fundraising campaigns continue to offer a far more reassuring vision, signalling to potential donors that conquest is imminent. “Cancer can be beaten … conquer cancer … end cancer … a future without breast cancer” are among the hopeful messages. No one doubts the importance of generating research dollars, but some critics question the marketing approach.

“They have no right to talk about [curing cancer],” said Sholom Glouberman, founder of the Patients’ Association of Canada. “I think it’s more than a bit misleading.”

Dr. Neel maintains that it’s possible that within two decades that significant treatments will emerge even for those now-incurable, metastatic cancers, though he predicts the end will come via a series of small victories: “with a whimper, not a bang.”

In his Pulitzer-winning book, The Emperor of all Maladies, oncologist Siddhartha Mukherjee is generally optimistic about the fight against cancer, but disavows the notion that a penicillin-like cure is imminent — or might ever come.

“Much of the battle will remain the same: the relentlessness, the inventiveness, the resilience, the queasy pivoting between defeatism and hope … the arrogance and the hubris.”

As his family again struggles with cancer, Mr. Bradford is understandably more blunt, calling on science to emerge from its “bubble” and recognize that it needs to aggressively pursue new ideas.
“Is the war on cancer going too slowly?” he said. “I’d say it’s like Afghanistan. There’s no way to win the way they’re doing it now.”

tblackwell@nationalpost.com
National Post

Labels: Biology, Health, Medicine, Science

posted by Pieface @ Saturday, March 16, 2013