Patients lacking for drug trials Shortage of volunteers to test new therapies hampers cancer studies; Recruiting a struggle

THE BALTIMORE SUN

Despite a sudden wave of progress in cancer research, scientists say their efforts are often slowed by struggles to recruit patients for the experiments that ultimately show whether new therapies are winners or duds.

It's the flip side of an encouraging story that captured the public attention in recent weeks.

Decades of slow, laborious study have led to new ways of preventing or treating the nation's second-leading killer disease. In the past month, scientists have reported success in preventing breast cancer with the drugs tamoxifen and raloxifene, shrinking advanced tumors with herceptin and treating early cancers with taxol.

What the public doesn't perceive, however, is that many trials go begging for volunteers. While the recent news prompted many cancer patients to ask their doctors about the drugs, researchers don't expect to have an easier time recruiting people for new studies.

Those involved in the tamoxifen trial said the slow pace of recruitment was one factor, though not the only one, that caused it to take five years rather than the two to complete.

"I talked to women's associations, gave talks at night, talks in the daytime, went to every hospital and every clinical center," said Dr. George Elias, a Baltimore cancer surgeon who ran the study locally. "I advertised the trial, put it in magazines, talked to the old women, talked to the young women -- and all I got were 75 people throughout the state of Maryland."

Ultimately, the trial attracted 13,000 from the United States and Canada. The results were so impressive -- a 45 percent reduction in cancer risk -- that researchers decided they didn't need to meet their original target of 16,000 women.

Researchers' problems

Elias, who works for the Helix Health System, started enrolling volunteers at his former post at the University of Maryland Medical Center, said he encountered problems that many researchers face.

Private doctors didn't want to recommend a drug that might not work. Some patients were scared by reports that the drug could increase their risk of uterine cancer; others were eager to get the drug, but bowed out when they learned they might get a placebo instead.

Of the 7 million Americans who have been diagnosed with cancer in the past five years, only 3 percent have participated in clinical trials. Researchers say progress would come faster if more people enrolled, but recognize that many patients turn away because they fear becoming a guinea pig in a scientific experiment that might not help them.

Experimental vs. better

Dr. David Golde, physician-in-chief of Memorial Sloan-Kettering Cancer Center, says doctors should be honest enough to explain the limitations of clinical trials. The public, he said, is often misled into thinking that "experimental" means "better." In the end, most progress is incremental. Many treatments fail, and others trade a few months of survival for harsh side effects.

"These are toxic, unproven drugs that are being tried, and many of them don't work," Golde said.

In the end, a drug must prove its value in a head-to-head contest with standard treatment. Many patients are desperate to try an experimental drug, but reject the idea that a virtual coin toss will determine whether they get a new drug or standard therapy that may not offer much hope.

Patients' misconceptions

This very problem has delayed progress of three experiments aimed at showing whether bone marrow transplants can extend the lives of breast cancer patients. Doctors in the federally funded trial just finished recruiting several hundred people for the trials. But the process took eight years -- twice the time originally planned.

"Many doctors and patients believed that bone marrow transplants were the right way to go, and they didn't want to be randomized in a trial where half got it and half didn't," said Dr. Nancy Davidson, who heads breast research at the Johns Hopkins Oncology Center.

Not wanting to leave anything to chance, many women learned they could get the transplants by "going outside the study." This means they got treated at medical centers that already offered the transplants for leukemia, lymphoma and some other conditions, and more recently treated breast cancer patients as well.

Many patients mistakenly believe that entering a trial means they risk forgoing treatment, according to researchers. Placebos are commonly used in trials involving healthy patients, such as the recent tamoxifen study. In studies of sick patients, however, new drugs are usually measured against standard therapy. In a typical experiment, one group might get traditional chemotherapy while the other would get the chemotherapy plus something else.

"So much of what goes on in clinical trials is in fact just routine care that would have gone on anyway," said Dr. Allen S. Lichter, president of the American Society of Clinical Oncology. But many patients don't understand that.

Another problem has been the refusal of insurance companies to pay medical costs associated with treatment.

Pharmaceutical companies and research grants typically cover experimental therapies, but patients are usually billed for hospital stays and other expenses stemming from complications.

This year, Maryland enacted a law requiring that insurers pay these costs. Only two other states have similar laws.

Patient's search

While researchers complain they can't find enough volunteers, many patients say they can't find trials that will accept them. Trials usually target a specific type of cancer at a specific stage -- even the number of lymph nodes to which cancer has spread.

A Pikesville woman, Michelle Proimos, discovered that getting into a clinical trial was like applying to college. The 37-year-old woman had already survived Hodgkin's disease, a condition for which there was an accepted treatment.

But when she was diagnosed with melanoma four years later, physicians gave her conflicting advice. She checked clinical trials on the Internet. But many excluded patients who had had cancer in the previous five years.

"I was at the four-year point [from Hodgkin's disease]. It just felt like I was so close," Proimos said. "It was hard, it was like you're not accepted."

With no other options, she began a standard treatment -- infusions of the drug interferon through a catheter in her chest wall. She had previously rejected this after hearing that many patients don't tolerate the high doses.

Two days after the catheter was inserted, Proimos was accepted into a trial of an experimental vaccine at Duke University. She abandoned the interferon treatment, and began monthly trips to North Carolina. So far, her progress is good.

Many patients say they waste precious time looking for trials because their personal physicians are poorly informed.

Some of this stems from "town-gown" tension, the sometimes rocky relationship between community physicians and their counterparts at academic medical centers.

"There are not that many doctors, health care providers who know about clinical trials," said Frances Visco, president of the National Breast Cancer Coalition. "They don't tell their patients about it. They're also concerned about proprietary issues -- they may not want to know because they may lose patients to the trial."

Some doctors, however, say patients just aren't aggressive enough.

"You see people who are very wired and searched the Internet, who come in with a print-out of 30 different clinical trials," said Dr. Barry Meisenberg, deputy director of the University of Maryland Greenebaum Cancer Center. "Other people come in and don't think to ask, 'Is there something else that might work better?' "

This year, the National Cancer Institute established a Web site that helps patients identify trials. The site contains more than 1,200 experiments run by the federal government, universities and pharmaceutical companies.

Companies are under no obligation to publicize their trials.

Two years ago, however, the Breast Cancer Coalition teamed up with Genentech, a large biotechnology company, to speed recruitment for its herceptin trial. The advocacy group publicized the trial in its newsletter, on Web sites and through its 450 member organizations.

"Too often, people don't know about the trials -- that's the primary reason why we got involved," said Visco.

Recruitment went quickly, and this month the company reported the surprising news that the drug had lengthened the lives of some women whose cancers had spread to other parts of their body. The drug is suitable for women with a genetic defect carried by a third of all breast cancer patients.

Experts predict that the drug will come on the market in the fall and could quickly become a standard treatment.

The address for the National Cancer Institute's Web site is http: //cancertrials.nci.nih.gov.

Pub Date: 5/31/98

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