HIGH-DOSE CHEMOTHERAPY AND AUTOLOGOUS STEM-CELL SUPPORT FOLLOWED BY POSTTRANSPLANT DOXORUBICIN AND TAXOL AS INITIAL THERAPY FOR METASTATIC BREAST-CANCER - HEMATOPOIETIC TOLERANCE AND EFFICACY

A multistep HDC regimen was designed as first-line chemotherapy for MB C, Twenty-four patients with MBC and no previous chemotherapy for meta static disease were treated with high-dose cyclophosphamide (5000 mg/m (2)), and etoposide (1000 mg/m(2)) (CyVP16), followed by granulocyte c olony-stimulating factor (G-CSF), Peripheral blood stem cells (PBSCs) were collected. Subsequently patients received cyclophosphamide (6000 mg/m(2)), thiotepa (500 mg/m(2)) and carboplatin (800 mg/m(2)) (CTCb) with hematopoietic rescue. Upon recovery from hematopoietic and gastro intestinal toxicity three cycles of doxorubicin (50 mg/m(2)) and taxol (150 mg/m(2)) were delivered. After CyVP16 42% of patients developed neutropenic fevers. There was one documented episode of bacteremia, Pa tients received CTCb 32 days after starting CyVP16, After CTCb the med ian number of days to ANC >5 x 10(9)/l was 10 and to a platelet count >20 x 10(9)/l was 14, Neutropenic fevers developed in 16 patients. The re were no hemorrhagic episodes. A total of 69 cycles of doxorubicin a nd taxol were delivered (87% of planned). The median time from PBSC in fusion to the first cycle was 38 days, The median time to the second c ycle was 27 days and to the last cycle was 24 days. One patient develo ped congestive heart failure. Two episodes of neutropenic fevers were observed. No toxicity-related deaths were observed. Grafts are stable at 6 months post transplantation. This multistep regimen is feasible w ith acceptable toxicity.