Breast Cancer Treatment Faulted

Two new studies published today confirm earlier findings that high-dose chemotherapy followed by a bone marrow transplant is not an effective way to treat breast cancer.

While the Dutch and American studies published in the New England Journal of Medicine found a longer time until relapse associated with the controversial treatment in selected women, they did not find an overall increase in survival.

The expensive and debilitating procedure was popular among women in the 1990s, but fell into disuse following several 1999 reports showing no benefit.

“For all of the hassle associated with the treatment, we are not getting a lot of bang for the buck,” said Dr. Derek Raghavan of USC.

“There’s a high level of morbidity and mortality associated with these treatments,” added Rebecca Garcia of the Susan G. Komen Breast Cancer Foundation. “You really have to question at what cost you are willing to continue these treatments.”

The chemotherapy-transplant combination was developed more than two decades ago and became popular in treating high-risk cases after preliminary studies appeared encouraging.

The idea is to use unusually high doses of anti-cancer drugs to kill as many breast cancer cells as possible.

These high doses also kill bone marrow cells, however, leaving patients at risk of anemia and infections. To avoid this, doctors follow the chemotherapy with a transplant of bone marrow cells collected either from the patient before chemotherapy or from a donor.

The mortality rate from the procedure initially ran as high as 20%. That rate has been reduced, but is still significant. And the procedure costs $100,000 to $150,000.

Results from four major clinical trials reported in 1999 showed no apparent benefit from the procedure. A fifth study by a South African researcher did purport to show a benefit, but an investigation found that he had fabricated his results.

Demand for the procedure dropped dramatically. As many as 10,000 chemotherapy-transplant procedures were performed in 1992, according to Dr. George Somlo of the City of Hope Medical Center in Duarte. “Today, there are a couple of hundred.” City of Hope used to perform about 80 per year, he added. Now it is fewer than 15, with the majority of those taking place in clinical trials.

“We put a lot of women through a terrible ordeal” that was not necessary or beneficial, said Susan Pisano of the American Assn. of Health Plans.

The new studies both started about 10 years ago. The U.S. study enrolled 551 women who were at high risk of recurrence because their cancer had spread to their lymph nodes. Half received the chemotherapy-transplant combination and half conventional chemotherapy. The Dutch study enrolled 885 similar women, half of whom received the controversial procedure.

The results “are consistent with previously reported studies,” Raghavan said. “There may be some progress in terms of a disease-free interval, but there’s no obvious benefit in terms of survival.” For a treatment this expensive and debilitating, “we need a home run. We need to have more patients cured. This is not a home run.”

The findings do “advance the field a bit,” Somlo said. He noted German researchers recently reported a small study in which women received the chemotherapy-transplant procedure twice and “did significantly better.” Newer drug regimens may also improve the results, he said.

With the small improvement in time until relapse “we can revisit the field and proceed with caution,” he concluded.