University of Pennsylvania Cancer Center
Last Modified: May 17, 1999
Analysis of data as of March 31, 1999, from the largest randomized trial of high-dose chemotherapy with stem cell transplant in the treatment of responding metastatic breast cancer has shown no significant difference in overall survival or lethal toxicity when compared to conventional dose maintenance chemotherapy. The study was led by Edward A. Stadtmauer and colleagues with the Eastern Cooperative Oncology Group and the University of Pennsyvlania Cancer Center.
The Philadelphia Bone Marrow Tranasplant Group (PBTG) activated this trial in december 1990 to compare overall survival, time to treatment failure, and toxicity in women with metastatic breast cancer whose disease was responding to chemotherapy. In 1995, the Eastern Cooperative Oncology Group (ECOG) assumed coordination of the PBT01 trial, as it became a nationwide study. The study design called for all patients to complete standard induction chemotherapy as the initial therapy. Those patients in response following this step and willing to proceed with the second step of the study were randomized to receive either high-dose chemotherapy with stem-cell transplant or conventional-dose maintenance chemotherapy. In the original design of the study, investigators based the size of the trial upon the assumption that the transplant regimen would be beneficial if the median survival for the patients who had complete response from induction therapy was extended from 2.5 years to 5 years and the median survival for those patients with partial response extended from 1 to 2 years.
Between 1990 and 1997, 553 women, aged 23 to 60 years old, were enrolled in the trial and receivede induction chemotherapy consisting of 4 to 6 cycles of either Cytoxan Adriamycin Fluorouracil (CAF) or Cytoxan Methotrexate Fluorouracil (CFM). Following completion of initial therapy, the patient population was re-evaluated. Of those women who had either complete or partial response following induction therapy, 199 women (median age of 46) agreed to continue to the seoncd stage of the trial. The remainder of the original 553 women either chose not to be randomized or were deemed ineligible because their disease had only stabilized or had progressed. Of the 199 pateints randomized, 184 were eligible for the analysis, (101 patients assigned to the high-dose chemotherapy/stem cell transplant regimen and 83 assigned to the maintenance chemotherapy). The median follow-up time is 37 months.
The results showed no difference in overall survival, regardless of complete or partial response to induction chemotherapy. The chart below shows the percentage of overall survival after three years between the two treatment arms and across the patient categories:
3-year Survival (Calculated from the Date of Randomization)
|All pts. |
|Compl. Resp. |
|Stem Cell Transpl.||32%||42%||27%|
No significant difference was seen betwen the two treatments for time to progression of their disease (median time to progression was 9.6 months for stem cell transplant and 9.0 months for conventional chemotherapy.) There was no significant difference in lethal toxicities between the two treatments. One treatment-related death was reported in a patient who had received a transplant.