Pursuing a balance of hope, help, data

Researchers struggle to care for individuals while completing tests

September 02, 2001|By Julie Bell | By Julie Bell,SUN STAFF

Roseann Bonanni would relive the moment. It would come to her as she lay in bed, and as she rode the train to work the next morning. It would seep into her thoughts as she wore her white hospital coat.

A desperate lung-cancer patient was sobbing after being told she didn't qualify for an experimental drug being developed by EntreMed Inc. of Rockville. She had already rejected chemotherapy, fearing it would induce nausea and other brutalities that would make it impossible to care for her children. EntreMed's drug, Angiostatin, appeared to have no side effects. Bonanni held her hand, consoling her, telling her of options.

"When patients read about these drugs, they think `This is the answer,'" said Bonanni, a research associate who signs up and monitors patients in human tests of experimental drugs. But Bonanni knows better.

Sometimes, as she talks to patients considering the drugs, trying to - in her own words - "sell" them on taking one, she feels she is playing God.

Like Bonanni and her colleagues at Thomas Jefferson University Hospital in Philadelphia, other medical workers walk a fine line as they usher patient volunteers through this country's thousands of clinical trials, as the human tests of drugs are known. They aim to nurture hope but not illusions, weigh patients' needs and safety along with the risks, weave urgency and deliberateness. It is a job that requires dispassionate science and compassionate medicine.

At Thomas Jefferson, radiation oncologists Walter Curran Jr. and Adam Dicker, nurse Anne Delengowski and Bonanni, a certified clinical researcher, daily navigate such conflicts as they oversee a trial that combines radiation with Angiostatin, which is designed to starve tumors by blocking the formation of blood vessels that feed them.

The trial, one of about 50 in the hospital's radiation oncology department, is generating some of the first data in a series of tests that will determine whether the Food and Drug Administration approves the treatment.

EntreMed, the researchers and, not least of all, the patients have big stakes in how the tests turn out. Ultimately, so does everyone who will be touched by the scourge of cancer.

Without such tests, breakthrough treatments would not exist. In May, the FDA rushed approval of Gleevec for a form of leukemia after it produced seemingly miraculous reprieves in once-dying patients. Over time, hospitals that handle similarly successful trials can build reputations as cutting-edge institutions, drawing more patients, building revenue and attracting top-notch medical staffs.

Doing clinical trials "links to the lab, it links to the clinic, it links to reputation," said Dr. Frederick J. Meyers, chairman of the department of internal medicine at the University of California-Davis Medical Center and an investigator who participated in trials that revolutionized testicular cancer treatment. "It attracts the best and brightest doctors."

But Meyers said doctors feel enormous pressure from drug companies and the government - when it is paying for drug research - to quickly enroll patients and generate data. Doctors must be careful, he said. "We can't treat people like mice and numbers."

Adding to the strain, medical staffs must balance trial requirements with a host of other responsibilities, from teaching medical students to handling full patient loads. Amid all this, they must take care to neither encourage false hopes nor dash patients' optimism as they press to find volunteers for a trial.

The challenge is amplified with Angiostatin, a drug that - along with sister drug Endostatin - created a sensation among cancer patients in 1998 after The New York Times reported that they had eradicated tumors in mice. One result: The Dana-Farber Cancer Institute in Boston had to devise a lottery to choose 15 patients from among the 1,861 who registered for an initial Endostatin trial in 1999.

Thomas Jefferson University Hospital, endeavoring to avoid such a surge, initially kept publicity about its Angiostatin trials to a minimum.

Sensation or not, even the most promising drugs are unlikely to show much effect in a Phase I trial like the one Thomas Jefferson is offering. That's because the first group of patients to get a new drug are given extremely low doses to ensure it doesn't hurt them. Even at higher doses, the first-stage trials are designed to test for safety - not effectiveness.

This remains on Bonanni's mind as she talks with patients, even in the trial in which Angiostatin is paired with the proven treatment of radiation.

"The lower dose levels are difficult for me to sell," she said. "You've got to make sure you're not falsely leading the patient."

Difficulty finding patients

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