Bone cancer information

Many people think that a bone-marrow transplant (BMT) is state-of-the-art therapy for breast cancer. In fact, it's not a treatment but instead a way of using the patient's own bone marrow to rescue her from otherwise lethal doses of chemotherapy. The procedure is costly, controversial, and traumatic and is not as successful as some research physicians had hoped.

Fortunately, the vast majority of women who have breast cancer won't even have to consider having a BMT. (See sidebar on page 5.) Approximately 182,000 women will be diagnosed with the disease this year, but only about 2,500 will have a BMT. At first, use of high-dose chemotherapy and BMT was reserved for women whose disease had spread (metastasized) to other organs. It seemed worth a try given that only about 18% of them survive five years with conventional treatment. Because the outlook is only somewhat better for women who have 10 or more cancerous lymph nodes, researchers are conducting clinical trials to see if high-dose chemo and BMT might help them as well.

About 15 years ago oncologists began to notice that women with advanced breast cancer who received higher doses of certain cancer-killing drugs were more likely to live longer. But they could only give so much before these highly toxic drugs eradicated the bone-marrow cells that produce blood cells needed to sustain life. Researchers decided to replace these lost cells with a BMT - a technique already being used successfully to treat Hodgkin's disease, nonHodgkins' lymphoma, certain leukemias and brain tumors, and testicular cancer.

High expectations

In the 1980s, studies of breast cancer patients given BMTs after high-dose chemotherapy showed that although a few women had short-lived or partial remissions, fatal complications were common. Despite this, women desperate for a cure began demanding the procedure even though there was no proof that it was more helpful than conventional chemo.

Hospitals and medical centers obliged. Between 1989 and 1994, more than 8,000 women with breast cancer underwent high-dose chemotherapy and BMT in the United States, according to the Autologous Blood and Marrow Transplant Registry in Milwaukee, Wisconsin. "Today any medium-sized or large city in the United States is likely to have a center that does BMTs for breast cancer," said oncologist Roy Jones, director of the bone-marrow transplantation program at the University of Colorado Health Sciences Center in Denver.

The regimen works for some women with advanced breast cancer. About one in five is alive and disease-free five years later and others gain another year or two of life without chemotherapy, according to Catherine Wheeler, an assistant professor of medicine at Harvard Medical School and a member of the bone-marrow transplant team at Dana-Farber Cancer Institute in Boston. But many aren't helped. Because the procedure has been in use for little more than a decade, long-term follow-up hasn't yet been possible.

What it's like

High-dose chemotherapy followed by bone-marrow rescue is carried out in several stages. In most cases, women undergo conventional chemotherapy first to see if their tumors are vulnerable to the cell-killing drugs. The next step is extracting and storing stem cells (precursors of other blood cells) from the patient's bone marrow (which requires general anesthesia), from circulating blood (which does not), or from both. Then high doses of chemotherapy drugs are given over four or five days. Afterwards, the patient's stem cells are reinfused so that she can once again manufacture blood cells.

Women who sign up for this treatment can expect to stay in the hospital for about a month, which accounts for much of the expense involved. The alternative is to shuttle back and forth between home and hospital for repeated infusions of chemotherapy that may last up to a year. For some women, a month in the hospital may be less disruptive.

High-dose chemo is the most risky part of the procedure, with a 1-5% mortality rate depending on where it's done. Chemotherapy causes intense, unpleasant side effects such as nausea, vomiting, bleeding, and diarrhea, and can also damage the stomach, heart, kidneys, and liver. The risk of infection is high until the bone marrow can regenerate enough white blood cells to protect the body.

Researchers are still tinkering with drug combinations and experimenting with adjunct therapies such as colony-stimulating factors that help bone-marrow cells regrow, antibiotics to fight infection, and better antinausea drugs.

Although the procedure has been in the news in recent years, it made headlines in March when the Dana-Farber Cancer Institute revealed that one woman died and another sustained severe heart damage after receiving a fourfold overdose of chemotherapy in December 1994. The women were taking part in a clinical trial for high-dose chemotherapy with bone-marrow rescue, which was halted when the mistake came to light.

A cheaper, gentler place

Researchers are currently evaluating the optimal place to do bone-marrow transplants. Oncologists at Duke University Medical Center have been able to cut costs and make women more comfortable by keeping them out of the hospital as much as possible. Between June 1992 and November 1994, 295 patients spent one or two days at the medical center for the bone-marrow harvest and four days for high-dose chemotherapy. Then 280 of the women recuperated at a hotel next door. Each day they attended a clinic for bone-marrow reinfusion and other care.

Forty-seven percent of the women never went back to the hospital, and 21% were readmitted for less than 24 hours due to infection or fever. Cutting the hospital stay from the usual 25 days to an average of eight days saved up to $70,000 per patient. And it made them much happier. "They preferred the privacy of a hotel, the ability to be in control, and the chance to have a friend or family member with them," said William Peters, director of Duke's BMT program.

Not something for everyone

Despite what news stories might suggest, not all women with advanced breast cancer are good candidates for high-dose chemo and BMT. "I don't think it's a treatment that every woman who has metastatic breast cancer should undergo," said Harvard's Dr. Wheeler, who is also clinical director of the bone-marrow transplant program at Beth Israel Hospital in Boston. Those who do well are in good health, have smaller tumors or limited metastases that responded to prior chemotherapy, and receive treatment early.

Women considering a BMT need to choose a doctor and medical center carefully. "It's very important that women feel a sense of trust and confidence in the doctor. They also need to look at experience and ask how many years the center has been doing transplants and how many procedures are done a year," said Dr. Wheeler. Dr. Jones noted: "If the patient were my wife, I would tell her to go somewhere that does more than 50 a year."

Waiting for answers

Women who seek out this high-profile treatment may not realize that it has not been tested in a head-to-head comparison with conventional chemotherapy. The National Cancer Institute is currently sponsoring two randomized trials comparing traditional chemotherapy with high-dose chemotherapy and bone-marrow support, but some researchers are having a hard time recruiting enough patients. That's because many hospitals already offer high-dose chemotherapy with BMT, so women who feel that this treatment is their only hope can get it without signing up for a study where they might be assigned to regular chemo.

Researchers are trying to overcome this problem. In one multi-center, randomized trial, high-dose chemotherapy and BMT will be compared with the highest dose of chemotherapy that can be given without bone-marrow rescue. "If it were really established that one treatment was better than the other, I wouldn't put women into the trial," said Dr. Peters, a professor of medicine at Duke. Results will be available in 1999.

To pay or not to pay

Already traumatized by learning that they have advanced breast cancer, many women are horrified by the news that their health insurance won't pay for a BMT, which can cost up to $150,000. The reason health insurers most often cite for denying coverage is that BMTs for breast cancer are considered to be experimental, according to a study published in the New England Journal of Medicine.

Out of 533 women who filed health insurance claims to participate in BMT clinical trials at Duke, 23% were denied coverage. Many insurers relent, however, when patients threaten to sue. In 1994, a California jury awarded $89 million in damages to the family of a woman whose health maintenance organization refused to pay for a BMT until it was too late.