Lack of adult patients thwarting cancer studies

Then it was his turn. The biggest barrier, in his opinion, was that almost no adult cancer patients — just three per cent — participate in studies of cancer treatments, mostly new drugs or drug regimens.

“To me it was obvious,” 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 Ramsey, Fred Hutchinson Cancer Centre in Seattle. He had brought up the subject he said no one wanted to mention. Forty years after President Richard M Nixon declared war on cancer, death rates have barely changed.

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, Ramsey and his colleague John Scoggins reported in a recent review.

Even worse, many that do get under way are pretty much useless, even as they suck up the few patients who participate. These trials tend to be small ones, at single medical centres. They may be aimed at polishing a doctor’s resume or making a centre seem at the vanguard of cancer care. But they are designed only to be ‘exploratory,’ meaning there are too few patients to draw conclusions or 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.

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 per cent to 80 per cent 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 receive 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.

Risk of legal liability

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.

Cancer experts offer two answers to the problem of clinical trials: spend more, giving doctors better incentives and perhaps even paying patients, or, with no real prospects for a big infusion of money, use available money and patients more efficiently.

Donald Berry, a statistician at MD Anderson Cancer Centre in Houston, wants to use resources more efficiently. To do so, he designed a new sort of study to test experimental drugs for breast cancer. The study starting this fall, is a departure from traditional notions of drug testing and cancer treatment.

Participants will be women who are newly diagnosed with breast cancer and at high risk that it will spread in their bodies.

Ordinarily, women with breast cancer have surgery first to remove the tumour in their breast and then have chemotherapy, which is the use of drugs to kill any remaining cancer cells. The problem with removing the tumour right away is that it can take five years to 10 years to know whether an experimental drug killed any remaining cancer cells. It is easier and much faster to assess an experimental drug’s effects on tumours that remain in the body. So in this study, women will get standard chemotherapy and experimental drugs first. Researchers will do MRI scans to see whether the tumours are responding.

Then, six months later, surgeons will remove the tumour or, if the tumour is gone, tissue from where it used to be, to determine how the cancer responded to the drugs.

The idea of leaving a cancer in place for six months can sound shocking, even dangerous. But cancer researchers say it actually makes no difference whether chemotherapy comes before or after surgery.

Also, this study will analyse the genetic makeup of the patient’s tumour and use that information to determine which drugs might be most effective. In most studies researchers have not accounted for genetic differences in tumours.

The new study will also ensure that women have a better chance of getting whatever drug seems to be working. As the study goes on, if one drug appears to be working better than others, researchers will adjust the study so that new participants whose tumours have the same genetic makeup will be more likely to get it.

The aim is to need much fewer women to determine whether a drug works, and get answers more quickly.

Berry said that some traditional breast cancer trials are seeking 5,000 or even 10,000 women. It is no surprise, he added, that trials start ‘limping along’ trying to enroll their quotas of patients.

In the new study, the winners of this drug competition will be tested in a definitive Phase 3 study with just 300 patients whose tumours have a similar genetic profile to those of the women who responded.

The New York Times