HIGH-DOSE BUSULFAN AND CYCLOPHOSPHAMIDE FOLLOWED BY AUTOLOGOUS TRANSPLANTATION IN PATIENTS WITH ADVANCED BREAST-CANCER

This study was conducted to evaluate the efficacy of high-dose busulfa n (BU) and cyclophosphamide (CY) in patients undergoing autologous hem atopoietic stem cell transplantation for metastatic breast cancer. Twe nty-two patients with stage IV breast cancer underwent autologous marr ow (n = 13), peripheral blood stem cell (PBSC) (n = 6) or marrow plus PBSC (n = 3) transplantation following BU (14-16 mg/kg) and CY (120-18 0 mg/kg), Of 22 patients, 18 had refractory relapse, one had primary r efractory disease, two had responding relapse and one had no evidence of disease (NED) at the time of transplant. Eight patients had bone on ly disease, six had bone plus visceral disease, and eight had locoregi onal recurrent disease, The median time from diagnosis to transplant w as 1124 days (range 210-2582). Staging for evaluation of response was performed 4-6 months after transplantation. Six patients were not eval uable (NE) for response because of MED at transplant (n = 1) or early death due to transplant-related complications (n = 5) (one of RSV inte rstitial pneumonia, two of fungal infection and two of regimen-related toxicities) occurring at a median of 17 days (range 14-59) post-trans plant. The patient who was NED at the time of transplant is still NED on day 336 post-transplant. Seven of the 16 evaluable patients achieve d a complete response (CR) (44%), five achieved a partial response (PR ) (31%) and five had no response (NR), with an overall response rate o f 75%. Five of 18 (28%) patients treated in refractory relapse, and bo th patients treated in responding relapse achieved a GR, Of the seven patients who achieved CR, three are alive and disease-free on days 204 , 276 and 752 and three relapsed on days 209, 715 and 1127 post-transp lant. One patient in CR died of aspergillus pneumonia on day 306 post- transplant. The median day to progression in five patients who achieve d a PR after transplantation was 335 (range 144-507). The probabilitie s of Survival and event-free survival (EFS) at 2 years was 0.22 and 0. 15, respectively for all 22 patients. The probability of EFS at 2 year s for the eight patients achieving CR (including one patient who was N ED at transplant) was 0.33, The probabilities of overall survival at 2 years in patients who did and did not achieve a CR after transplantat ion was 0.63 and 0.14, respectively (P = 0.004). These data suggest th at high-dose BU-CY followed by autologous stem cell transplantation is an effective regimen in patients with advanced breast cancer demonstr ating that BU is an active agent in this disease and could be incorpor ated into treatment regimens requiring hematopoietic stem cell support .