Interim Results of Large Trials of High-Dose Chemotherapy With Bone Marrow or Stem Cell Transplants for Breast Cancer

National Cancer InstituteEMBARGOED FOR RELEASE, Thursday, April 15, 1999, 9:00 a.m. ESTNCI Press Office

For the first time since the introduction of high-dose chemotherapy for breast cancer with bone marrow or stem cell transplants (HDC/BMT), patients and their physicians have data from large scientific studies comparing this treatment to standard therapies.

The new data come from five separate clinical trials, preliminary summaries of which were released April 15 by the American Society of Clinical Oncology (ASCO). In four of the five studies, investigators found no statistically significant difference in survival between patients receiving HDC/BMT and those receiving lower-dose chemotherapy without transplants. In the remaining trial, from South Africa, there was a significant difference in favor of HDC/BMT.

The five studies were all randomized, controlled (phase III) clinical trials, which directly compare one cancer treatment to another. Four of the trials (two in the United States, one in Scandinavia, and one in South Africa) each involved hundreds of patients and will be presented in a plenary session at ASCO's annual meeting, May 15-18, in Atlanta. The fifth trial, in France, involved fewer patients and will be presented as a poster session during the same meeting.

"The hypothesis going into these trials, our hope, was that the more aggressive approach would prove clearly superior to standard therapy," said Richard Klausner, M.D., director of the National Cancer Institute (NCI), which sponsored the two U.S. trials. "But based upon these studies, high-dose therapy has not yet been shown to be superior to lower-dose treatment. These studies do suggest it is at least equivalent in terms of overall survival, but the added toxicity and costs of high-dose treatment require that it be superior if it is to become a standard of care."

Klausner pointed out that the positive results of the smaller South African study should not be disregarded. "The chemotherapy agents used in this trial were different from those in the other trials and the particular approach employed by the South Africans may be responsible for the positive results," he said.

The five trials have added greatly to our knowledge, said Robert Wittes, M.D., director of NCI's Division of Cancer Treatment and Diagnosis. "Up to now, breast cancer patients have had to rely on results from small feasibility studies when making decisions about this aggressive therapy," he said. "Now they have the more reliable information that can be obtained only from phase III trials. The information from these studies, viewed collectively, does not suggest that high-dose chemotherapy with transplants improves survival."

Wittes did add, however, that "the duration of follow-up is still relatively short, additional data will continue to be gathered, and the results will need to be updated and re-analyzed at suitable intervals in succeeding years. He cautioned that " results might change with time for some of these studies."

Wittes also noted that the findings of these trials apply only to patients whose cancer has spread to other parts of the body or those at higher risk of relapse because the cancer has spread to many nodes. In addition, the results may not apply to other high-dose regimens.

These limitations raise important questions about future directions of clinical research and recommendations for patient care. "We expect that there will be lively discussion, debate, and even disagreement among physicians about the implications of these findings," Wittes said. "Some may consider the matter settled, at least for these particular patient groups, and will no longer consider high-dose chemotherapy with transplants worthy of further testing. Others will be more impressed with the limitations of the present trials and will be eager to continue studying different high-dose combinations."

NCI continues to support ongoing phase III studies of HDC/BMT in breast cancer, and it is possible that these may reveal an advantage for certain subsets of patients or for different high-dose regimens. For example, a national trial is now under way to test high-dose therapy in women who have only four to nine cancerous lymph nodes.

Another U.S. trial in women with 10 or more involved lymph nodes using a different high-dose regimen with transplant support has enrolled the required number of patients and results should become available in the next one to two years.

Many breast cancer patients currently receive high-dose therapy outside of trials. "Although particular circumstances may still lead physicians to recommend high-dose therapy for some patients, the NCI strongly encourages the use of well-designed clinical trials whenever possible," said Wittes. "Only in this way will we eliminate the uncertainties that continue to exist and improve outcomes for patients over today's standard treatment approaches."

Klausner also stressed the importance of participation in trials. "These five trials took nine years to yield these preliminary data because it took so long to enroll the required number of patients," he said. "Greater participation by physicians and patients in clinical trials would speed answers, not only to crucial questions concerning high-dose chemotherapy with transplants, but other cancer treatments as well."

It is important to note that HDC/BMT has been proven in clinical trials to be the most effective therapy in several other cancers, including certain kinds of leukemia and lymphoma. The results of the breast cancer trials do not apply to other kinds of cancer.

Summaries of the five studies and their findings are available on the ASCO Web site (http://www.asco.org). More detail will be available at the time of the presentations on May 17. Portions of the ASCO meeting, including these presentations, will be accessible through the organization's Web site.

More information is also available on the NCI's Web site for clinical trials (http://cancertrials.nci.nih.gov), including a questions and answers fact sheet on these studies.