Published: Monday, 3 Aug 2009 | 10:58 AM ET

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Not long ago, at a meeting of an advisory group established by Congress to monitor the war on cancer, participants were asked how to speed progress.

“Everyone was talking about expanding the cancer work force and getting people to stop smoking,” said Dr. Scott Ramsey, a cancer researcher and health economist, who was participating in that January 2008 meeting of the President’s Cancer Panel. “Lots of murmurs of approval.”

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Then it was his turn.

The biggest barrier, in his opinion, was that almost no adult cancer patients — just 3 percent — participate in studies of cancer treatments, mostly new drugs or drug regimens.

“To me it was obvious,” Dr. Ramsey said. “We can’t improve survival unless we test new treatments against established ones.”

The room fell silent.

“It was one of those embarrassing moments,” said Dr. Ramsey, an associate professor at the Fred Hutchinson Cancer Center in Seattle. He had brought up the subject he said no one wanted to touch.

Forty years after President Richard M. Nixon declared war on cancer, death rates have barely changed. “Why aren’t we getting cures?” Dr. Ramsey said. “This is one of the biggest reasons.”

Of course, there have been highly successful clinical trials — studies of drugs like Gleevec for chronic myelogenous leukemia and estrogen-blocking therapy for breast cancer, and also studies that proved drugs did not work. But the problem is still immense, cancer researchers agree.

There are more than 6,500 cancer clinical trials seeking adult patients, according to clinicaltrials.gov, a trials registry. But many will be abandoned along the way. More than one trial in five sponsored by the National Cancer Institute failed to enroll a single subject, and only half reached the minimum needed for a meaningful result, Dr. Ramsey and his colleague John Scoggins reported in a recent review in The Oncologist.

Even worse, many that do get under way are pretty much useless, even as they suck up the few patients willing to participate. These trials tend to be small ones, at single medical centers. They may be aimed at polishing a doctor’s résumé or making a center seem at the vanguard of cancer care. But they are designed only to be “exploratory,” meaning that there are too few patients to draw conclusions or that their design is less than rigorous.

“Unfortunately, many patients who are well intentioned are in trials that really don’t advance the field very much,” said Dr. Richard Schilsky, an oncologist at the University of Chicago and immediate past president of the American Society of Clinical Oncology.

Others studies, by companies, are designed to persuade doctors to use their drugs.

Still others are testing questions like whether it makes a difference to give a drug every nine days or every two weeks. “These are practical real-world questions,” Dr. Schilsky said. “But they don’t do a great deal to advance the research field. They are not going to provide the next breakthrough.”

In any case, the great majority of oncologists just steer clear of studies. They make little or nothing on trials and, in fact, often lose money. These doctors also may discourage patients from going elsewhere to enter a trial: if a patient leaves, the doctor loses business.

One issue is the money lost on chemotherapy, the source of 60 percent to 80 percent of the revenue at oncologists’ offices. The doctors buy the drugs and are reimbursed by insurance for slightly more than the drugs’ cost. But if patients are in clinical trials, the drugs may be paid for by the federal government or a drug company sponsoring the study — and doctors get nothing.

Then there is the poorly reimbursed hour or so it takes to explain a trial to prospective patients. And, after all that, most patients either turn down the trials or, after further testing, turn out to be unqualified.

That is just the start, cancer specialists say. There is voluminous paperwork. And the risk of legal liability for errors like neglecting to mention a financial interest in the drug being tested, in specimen handling or in billing.

“A lot of doctors say, ‘This is not worth it,’ ” Dr. Schilsky said.

Reluctant Patients

It is one of the worst times imaginable — a cancer diagnosis, all the terror that goes with it, and then, sitting in a doctor’s office and being asked to make difficult decisions about treatment. Then add questions about joining a trial. Some say it is just too much to think about.

Research starts with so-called Phase 1 trials that test a drug’s safety and the maximum dose patients can tolerate. Although it is possible that some will benefit, most do not because the doses are ineffective or unsafe and few new drugs prove worthwhile.

Then comes Phase 2, further testing of the drug in a small study, and Phase 3, in which patients with a particular cancer that is still treatable are randomly assigned to get the best available current drug or that drug plus the new experimental one.

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Most patients are not interested in clinical trials. Some do not want the extra office visits and tests a trial entails and do not want their treatment determined by the flip of a coin. Others fear getting a placebo, even if there isn’t one — placebos are rarely used in United States cancer trials. Others find the whole idea too overwhelming when they are trying to save their lives.

At California Cancer Care, in Greenbrae, north of San Francisco, where Dr. Peter Eisenberg works, the agony of choosing a trial was on display. Although the oncologists there try to offer trials to every patient, last year they enrolled just 43 of about 700 new patients.

The most enthusiastic have lethal tumors and no effective treatments, Dr. Eisenberg explained. They are like one of his patients, Ken Fye, a retired rheumatologist with pancreatic cancer who hopes to find a study in which he can enroll. He figures he has little to lose and wants to help science. “It would be obscene if I did not,” he said.

It is not entirely clear why some trials succeed, but researchers say those that do may have some features in common: patients may be like Dr. Fye, with no or few options, so they are easier to recruit, particularly if the drug promises to make a real difference, not just give them a few days or weeks. Successful trials also typically address an important problem, as opposed to a more marginal one, and involve experienced investigators and patient advocates who push for participation.

But it can be particularly hard to recruit patients whose prognosis is better.

Gael Casner, for instance, turned down a trial that would have required her to see Dr. Eisenberg for weekly infusions of a cancer drug, Avastin, that was being tested. It had helped women with breast cancer that was more advanced than her own.

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For Ms. Casner, a 57-year-old college admissions adviser, the prospects, after surgery and chemotherapy, were excellent. “I was thinking, ‘O.K., I hate shots,’ ” she said. And she has to travel for her job, making it difficult to go in once a week for an infusion.

“If they had said every month, I would do it,” Ms. Casner said. “But every week was a deal breaker. That was why, personally, for me, the trial did not make sense. I was not in a life-threatening situation.”

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