HIGH-DOSE CHEMOTHERAPY WITH CARBOPLATIN, ETOPOSIDE AND IFOSFAMIDE FOLLOWED BY AUTOLOGOUS STEM-CELL RESCUE IN PATIENTS WITH RELAPSED OR REFRACTORY MALIGNANT-LYMPHOMAS - A PHASE I II STUDY/

Patients with relapsed or refractory non-Hodgkin's lymphomas (NHL) and Hodgkin's disease (HD) with recurrences after an anthracyclin-contain ing regimen only have a chance of cure of below 10% with conventional chemotherapy. In order to improve their prognosis, we started a phase I/II trial using high-dose therapy comprising carboplatin, together wi th etoposide and ifosfamide (CEI), followed by autologous stem cell re scue (ASCR) as consolidation after salvage treatment. Since September 1990, 40 patients with intensively pretreated advanced NHL (n = 24) or HD (n = 16) received one cycle of high-dose therapy (HDT) consisting of carboplatin 1500 mg/m(2), ifosfamide 10 g/m(2) and etoposide in esc alating doses from 1200 mg/m(2) to 2400 mg/m(2) followed by ASCR. Thir ty-nine patients were assessable for toxicity and response. The follow ing doses appeared to be safe: carboplatin 1500 mg/m(2), etoposide 240 0 mg/m(2) and ifosfamide 10 g/m(2). All patients developed grade 3 nau sea and grade 3 or 4 mucositis. Granulocytopenic fever occurred in 100 % with grade 4 infections in 15%. Mild transient kidney toxicity was n oted in 36% and liver toxicity in 20% of patients. One toxic death occ urred (2.5%). Objective responses were obtained in 36 of 39 patients ( 92%) with complete remissions (CR) in 24 patients (61.5%) and partial remissions (PR) in 12 (30.7%). Median observation time for surviving p atients was 23.3 months (range 3.4-52.3). The probabilities of overall , event-free and relapse-free survival at 2 years are 62, 39 and 55%, respectively. Patients with primary refractory disease or resistant re lapse had a poor prognosis. High-dose carboplatin, etoposide and ifosf amide plus autologous stem cell rescue represents an effective, potent ially curative salvage treatment with acceptable toxicities.