PHASE I II TRIAL OF CARBOPLATIN DOSE-ESCALATION IN COMBINATION CHEMOTHERAPY WITH ETOPOSIDE, BLEOMYCIN AND GM-CSF SUPPORT FOR POOR-PROGNOSISNONSEMINOMATOUS GERM-CELL TUMORS PATIENTS/

To determine the maximum tolerated dose (MTD), and therapeutic efficac y of carboplatin (CBDCA) in combination with etoposide and bleomycin ( CEB) as initial chemotherapy for poor prognosis germ cell tumors, a CB DCA dose escalation supported with GM-CSF had been performed. Twenty f our untreated patients were treated with CBDCA 400 mg/m(2) on day 1, e toposide 100 mg/m(2) on days 1 to 5 and bleomycin 30 mg on days 1, 3, 5. Four cycles were scheduled at 21-day interval. The first cohort of 6 patients received only initial chemotherapy regimen. In the subseque nt cohorts of six patients, the CBDCA dose was increased by 100 mg/m(2 ). A fixed dose and schedule of GM-CSF at 5 mu g/kg subcutaneously was given on days 6 through 15. Myelosuppression, with neutropenic fever and hemorrhages, was the dose-limiting toxicity at the 600 mg/m(2) dos e level. The recommended dose of CBDCA is 500 mg/m(2). Overall complet e response (CR) rate was 71% and with median follow up of 25 (16-34) m onths, 58% of patients are alive and have no evidence of disease (NED) . A higher number of CR was achieved with CBDCA dose higher than 400 m g/m(2) compared with CBDCA dose of 400 mg/m(2) (92 vs. 50%, p = 0.03), as well as a higher proportion of patients who are alive and with NED (75 vs. 42%,p = 0.1). Despite GM-CSF support, the MTD of CBDCA could not be increased beyond 500 mg/m(2) (50% of the dose escalation), due to severe myelosuppression. The treatment outcomes obtained with CEB i n our study are no better than the standard cisplatin-based chemothera py. Further studies of this regimen, where CBDCA dose should be calcul ated according to the patients glomerular filtration rate are warrante d.