Controversial Therapy Proves No Better Than Traditional for Metastatic Breast Cancer
Citing the clinical importance of the study findings, the editors of the New England Journal of Medicine released the results today, in advance of publication April 13. The findings help to clear the muddy water on the purported benefit of a popular, but not rigorously tested, regimen over traditional multiple-drug therapy.
The decade-long multicenter study involved women, ages 30-61 years, whose breast cancer had spread to other sites but who had not previously received chemotherapy for metastatic disease. Patients initially received four to six cycles of combination therapy to induce remission of the cancer. Those patients whose disease had completely or partially responded to this treatment were then randomized to receive conventional-dose chemotherapy for up to two years or to undergo stem-cell harvest from the bone marrow followed by high-dose chemotherapy over four days and then transplantation of the stem cells.
Of 553 enrollees in the study, only 199 women completed the treatment protocol. Because of problems with eligibility, only 184 women were included in the primary analysis of treatment efficacy and safety. Twenty of these women refused to proceed with the treatment assigned to them. The 10 women who refused conventional-dose chemotherapy and requested stem-cell transplantation suffered relapse of their disease, and 8 of them died.
During a planned interim analysis, the committee monitoring the data determined that the study had a very low likelihood of showing results favorable to stem-cell transplantation. Final analysis of the data showed that 114, or 62 percent, of the women had died.
The two study groups did not differ significantly in the median length of patient survival and the percentage of women surviving three years, with the entire group of 184 women having a median survival of 25 months and a three-year survival rate of 33 percent. Patients who had been in complete remission at the time of randomization to treatment consistently had a higher survival rate, but these rates did not differ significantly between the two treatment groups. Time to progression of the cancer also did not differ between the two treatment groups.
Leukopenia and thrombocytopenia developed in 96 percent and 95 percent of the patients who underwent stem-cell transplantation. Patients who received conventional-dose chemotherapy fared much better, with leukopenia developing in only 52 percent and other adverse effects occurring in 6 percent or less.
The research team, led by the Philadelphia Bone Marrow Transplant Group, urged the medical community not to extrapolate the study findings to patients with breast cancer who have multiple positive axillary lymph nodes but no metastases.
In an accompanying editorial, Marc E. Lippman, M.D., cautioned that the "disappointing results" from the study "in no way indicate that variations on this theme may prove unsuccessful." Lippman, who directs the Lombardi Cancer Center's Breast Cancer Program, in Washington, D.C., noted that the "astounding benefits" reported in previous studies of high-dose chemotherapy plus bone marrow transplantation for metastatic breast cancer came from uncontrolled trials. He advised clinicians to turn now to "well-justified alternative experimental approaches," such as successive transplantations, under study in clinical trials.