Originally created 05/18/99

Some breast-cancer experts hold out hope for bone-marrow transplants



ATLANTA -- Some experts say grueling bone marrow transplants for advanced breast cancer will eventually prove worthwhile, despite disappointing results from some long-awaited studies.

Over the past decade, doctors have increasing urged women with advanced breast cancer to undergo extremely high doses of chemotherapy in a last-ditch attempt to stop their disease. The treatment is so toxic that it kills the bone marrow, so patients need marrow transplants to restore their bodies' ability to make blood cells.

While this treatment clearly can cure leukemia and lymphoma, there has been no solid evidence that it actually improves the outlook for breast cancer, despite its wide use.

The start of an answer was expected to emerge from five studies being conducted in the United States, Europe and South Africa. However, their results are unsettling for both doctors and patients.

While the findings do not prove this approach works, they also do not mean it should be abandoned.

Brief summaries of the results were released last month, and the presentation of more detailed reports was the leading topic Monday at the annual meeting of the American Society of Clinical Oncology, the world's biggest gathering of cancer specialists.

Doctors who have long advocated intensive chemotherapy for this disease pointed out glimmers of good news in the generally dismal results, and they still recommend it. Others say the data should eliminate any pressure on women to go for the most difficult treatment.

"There has been a lot of hype about the benefits of bone marrow transplants without any clear evidence," said Dr. Derek Raghaven of the University of Southern California. "These date will remind women that they have a choice."

Raghaven and others at the conference predicted that high-dose therapy followed by marrow transplants will be done less frequently, at least until new data emerge showing that the approach actually saves lives.

"Doctors and patients are rethinking the use of transplants," said Dr. Edward Stadtmauer of the University of Pennsylvania.

Since the mid-1980s, more than 12,000 women with breast cancer in the United States have undergone bone marrow transplants. In about 5 percent of cases, the treatment itself is fatal.

At first, the approach was limited to women with clearly spreading breast cancer. But now more than half the time it is used for those whose outlook is somewhat better -- those whose cancer has spread to several lymph nodes but cannot be found in other parts of their bodies.

The new data are difficult to compare since the studies involve different combinations of drugs and varying severity of disease. However, the data look especially unfavorable for women with spreading cancer.

In the largest study ever among these women, Stadtmauer and others randomly assigned 199 to undergo standard chemotherapy or the high-dose approach. Three years later, there was no difference in their survival. A similar but smaller French study also found no survival difference after five years.

However, results were somewhat less clear for women with cancerous lymph nodes but no clear spread. Typically, doctors give these women standard doses of chemotherapy followed by high doses.

A South African study involving 154 women suggests this approach might be wrong. By eliminating the initial low dose and giving women high-dose treatment from the start, they appeared to double survival after five years.

Two other studies that took more conventional approaches and saw no difference in survival after two or three years of follow-up. Still, some details pointed to a possible advantage of high-dose chemotherapy.

In the largest of the studies, 22 percent of the women getting high-dose treatment had relapsed after three years, compared with 32 percent getting lower doses. Even though their survival was the same, longer follow-up may still show the high-dose patients do better.

"You can't say somebody is cured of breast cancer for 20 years," said Dr. Karen Antman of Columbia Presbyterian Medical Center in New York City. "It's way too early. We have to wait."

For the average cancer patient, the decision until then will come down to a willingness to undergo a risky treatment for a benefit that is uncertain and perhaps even nonexistent.

"We have five times the information than we had up to now," said Dr. Gabriel Hortobagyi of the University of Texas M.D. Anderson Cancer Center in Dallas. "This is still far less than we need."