Photo by Gordon Todd
Victoria Wolfe was confident that her suspicious lab results were nothing to worry about. A busy mother of two young daughters, she recently had relocated to the West Coast, where she had just begun to explore work options and the Northern California countryside.
Her doctor's concern, though, was that Wolfe's leukemia - in remission for the last year thanks to intensive combination-drug therapy - had returned.
"The doctor urged me to just check things out," she remembered. "I was feeling very positive."
On her doctor's advice, Wolfe traveled to Seattle in late 1998 to consult with an oncologist at the center, where her worst fears were confirmed. Her disease, a rare cancer known as acute promyelocytic leukemia, was back.
"My life was blown out of the water," she said. "But I was prepared to have a bone-marrow transplant immediately, having already identified my brother as a donor when I had first gotten sick."
The transplant would have to wait. A lung biopsy to investigate a suspected fungal infection left Wolfe too weak to proceed with the treatment. Her only option was to aggressively fight the leukemia with drugs with the hope of inducing a second remission, which would make her a better candidate for a successful transplant.
Her condition rapidly worsening, Wolfe elected to try an experimental drug, arsenic trioxide, recommended by Fred Hutchinson doctors. The drug had shown promise in inducing remission in a small preliminary study at another cancer center.
From conversations with her doctor as well as her own research, Wolfe knew that the treatment wasn't a sure thing. With so few patients previously treated with the drug, many of Wolfe's questions about the therapy had yet to be answered.
"Most of us in this situation choose a clinical trial because we have no other options, no other hope left," she said. "But there was never any question that the decision to choose this treatment was all mine."
Two years post-transplant, Wolfe recently completed a book on her experience with cancer in which she credits both her faith and scientific research for getting her through.
"There's no question in my mind," she said. "The arsenic-trioxide clinical trial saved my life."
Wolfe is one of hundreds of critically ill patients each year who consult doctors at Fred Hutchinson. They come seeking their best chance for a cure for a fatal disease. By choosing to take part in a clinical trial, they also may give life to thousands of others similarly diagnosed.
The National Cancer Institute says that each year about 23,000 cancer patients - only about 3 percent of all diagnosed - take part in an institute-sponsored treatment clinical trial. In such studies, patients help doctors find ways to improve cancer therapies. At the same time, they gain access to cutting-edge care that may increase their chances for survival compared to standard therapies. Medical progress can't be made without these doctor-patient partnerships, which, say many cancer experts, number far too few.
Dr. John Crowley, a Public Health Sciences Division researcher and director of the statistical center for the Southwest Oncology Group, an NCI-funded cooperative that conducts large-scale, national clinical trials, said poor patient recruitment is a major reason many studies close early.
"About 10 percent of our trials close because of inadequate patient accrual - not because we discover a treatment isn't working," he said. "That means many important questions about cancer treatment go unanswered."
The phrases "clinical trial" or "experimental therapy" may conjure up images of impersonal and inferior health care that deter many who might benefit most from choosing these options. A Harris survey of 2,000 American adults earlier this year confirmed that such fears are widespread. While most Americans feel clinical studies are essential for testing new therapies, only 32 percent of those polled were very confident that participants get good medical treatment.
But those like Leanne Looney, who elected to participate in research, recount experiences that reflect compassionate, attentive care. Looney's daughter, Alyson, was 8 months old when she was diagnosed with acute lymphocytic leukemia.
"Imagine your worst nightmare magnified five times," she said. "We were told there was no alternative and that past research had shown only 1 in 17 children with the same disease characteristics had survived more than five years with conventional chemotherapy alone."
After successfully completing six months of chemotherapy treatment, Alyson received a bone-marrow transplant in late 2000 in a clinical trial developed by Fred Hutchinson doctors. She was treated at the Seattle Cancer Care Alliance pediatric transplant ward at Children's Hospital and Regional Medical Center. Looney said any notions of impersonal care were immediately dispelled.
"We felt as though we were put on a pedestal," she said. "I felt like Alyson was the only patient at the hospital. People went out of their way to be helpful and kind and attentive."
Success stories like Alyson's are largely the result of the center's "bench to bedside" approach to research. Almost all practicing physicians on staff also conduct research, allowing new treatments to move quickly to patients.
Dr. Fred Appelbaum, director of Clinical Research Division and the Alliance, said that although such dual careers present logistical challenges, the ultimate benefit to patients is enormous.
"Nothing motivates you in the lab more than knowing that your research may have a direct benefit in the clinic, and nothing informs your research like seeing patients," he said.
"Our physicians work in the clinic on a rotating basis to allow us to spend time in the laboratory. We know sometimes this can be difficult for patients, but both research and patient care take enormous concentration. It would be unfair to patients to try to do both simultaneously - and patients ultimately reap great reward from our ability to do research."
The fruits of this investigation are new therapies that, after careful tests in the laboratory and on animal models, must be tested on patients in research studies to prove their ultimate worth.
Despite stringent federal regulations to protect patient safety, however, many potential participants have fears about inadequate information on the risks and benefits of clinical trials. The Harris survey found that only 25 percent of those polled are very confident that patients are thoroughly informed of the risks in a research study.
In fact, extensive legal requirements ensure that patients on clinical trials make informed choices about their care. And because participants are closely monitored throughout their treatment, they often feel they receive more information about their disease and therapy than they otherwise might with standard care.
Being on the receiving end of so much honest information, Wolfe said, can sometimes be like "taking bullets."
"It's a real conundrum for doctors to present all of the possible risks and side effects of an experimental treatment and yet leave the patient with some hope," she said. "But it's their responsibility to be very frank with the patient and to make sure that the patient is the one to decide whether to participate."
The critical step
The critical decision-making step in a clinical trial takes place during an informed consent conference. At this meeting, a health-care team, including a doctor, nurse and social worker, meet with a patient and their family to review the diagnosis, discuss options and alternatives and, ultimately, oversee signing of consent documents.
Such conferences routinely last hours, with patients and family members asking questions and taking detailed notes. Patients are informed of survival statistics for a given treatment and are walked through each step of a procedure, including the best and worst they can expect to encounter.
Often, a patient is asked whether he or she wants to participate in additional research studies outside of their treatment. Such studies, Appelbaum said, might be long-term analyses to assess which patients ultimately develop infections or other complications.
"These are typically additional blood draws, performed at the same time a patient is having blood taken to monitor their condition, that pose neither a risk nor direct benefit to the patient - and patients are free to decline participation," he said. "But they may be of future benefit to other patients. This is how we've gotten to where we are today, in terms of the success of our treatment."
By the time any trial enrolls patients, all aspects of the research have been scrutinized by an extensive series of committees that certify the scientific validity of the research and ensure all treatments meet humane, ethical guidelines.
The culmination of this process is approval by an institutional review board, a federally mandated committee of scientists, medical experts and community members who review all new, proposed human-subject research to assure that the rights and welfare of the research participants are protected. The board also reviews active, approved studies and has the power to halt a trial at any time if preliminary results are show little or no benefit.
The thorough exchange of information between patient and medical professionals continues throughout treatment. In addition to contact with their physicians, Fred Hutchinson patients are treated by a health-care team that includes research nurses, a social worker, a nutritionist and other support staff.
Research nurses observe patients for side effects, draw blood for tests, administer drugs and coordinate patients' overall care. They often see their primary role as that of a patient advocate, said Kathleen Shannon Dorcy, a research nurse who has cared for Fred Hutchinson patients for more than 15 years.
"Patients are here for so long, you develop a relationship," she said. "I'm often asked by patients, 'What should I do?' One of my roles is to help them reaffirm that they can make the decision themselves."
Victoria Wolfe credits Shannon Dorcy and her team of doctors for their willingness to listen to how and why she made decisions about choosing to participate in clinical trials.
"This truly contributed to a collaborative process," Wolfe said. "These discussions were just a few of the countless moments at Fred Hutchinson when someone respected my decision-making process and encouraged me. I was not simply another patient. It's really a miracle to me."