A PHASE I-II STUDY OF HIGH-DOSE MELPHALAN, MITOXANTRONE AND CARBOPLATIN WITH PERIPHERAL-BLOOD STEM-CELL SUPPORT IN PATIENTS WITH ADVANCED OVARIAN OR BREAST-CARCINOMA

The purpose of this study was to develop a high-dose chemotherapy (HDC ) and peripheral blood stem cell (PBSC) regimen for treatment of patie nts with ovarian carcinoma that could be administered in an outpatient setting, Fourteen patients,vith advanced ovarian (n = 9) or breast (n = 5) carcinoma, who had failed conventional chemotherapy, were entere d into a dose-escalation trial to determine the maximum tolerated dose (MTD) of carboplatin that could be administered with fixed doses of m elphalan (160 mg/m(2)) and mitoxantrone (50 mg/m(2)), Twenty-five addi tional patients were included in a phase LI trial at the MTD, Two of t wo patients had grade 4 severe regimen-related toxicities (RRT), one f atal, at a dose level of 1600 mg/m(2), Two of 29 patients (6.9%) treat ed at the MTD (carboplatin, 1400 mg/m(2)) died of RRT, All three patie nts who died of toxicity had a calculated AUC for carboplatin >30 mg/m l/min. Thirty-one patients with ovarian cancer who had failed chemothe rapy were treated, 24 at the MTD, Fourteen of 20 patients (70%) with o varian carcinoma with evaluable disease achieved a CR and seven (35%) are alive disease-free a median of 20 months (range, 7-26), Five of se ven patients with ovarian cancer who had failed chemotherapy but were rendered clinically disease-free following surgery survive without pro gression a median of 13 months (range, 9-19), Eight of 16 (50%) platin um-resistant and 4/12 (33%) platinum-sensitive patients with ovarian c ancer survive disease free.