A RANDOMIZED TRIAL OF CISPLATIN, ETOPOSIDE AND BLEOMYCIN (PEB) VERSUSCARBOPLATIN, ETOPOSIDE AND BLEOMYCIN (CEB) FOR PATIENTS WITH GOOD-RISK METASTATIC NONSEMINOMATOUS GERM-CELL TUMORS

Background: Cisplatin-based combination chemotherapy will cure 70% to 80% of patients with metastatic non-seminomatous germ cell tumors but is associated with the possibility of severe neuro-, oto- and nephro-t oxicities, Carboplatin, a cisplatin analogue, is an active drug in tes ticular cancer with a more favourable spectrum of side effects. In a r andomized trial, the German Testicular Cancer Study Group compared a c ombination regimen of carboplatin, etoposide and bleomycin (CEB) to st andard cisplatin, etoposide and bleomycin (FEB) chemotherapy for patie nts with 'minimal-' and 'moderate-disease' non-seminomatous germ cell tumors, according to the Indiana University classification. Patients a nd methods: FEB was given for three cycles at standard doses (given da ys 1-5), and the CEB regimen consisted of carboplatin (target AUC of 5 mg/ml x min) on day 1, etoposide 120 mg/m(2) on days 1 to 3 and bleom ycin 30 mg on days 1, 8 and 15. Four cycles of CEB were given, with th e omission of bleomycin in the fourth cycle. Thus, the cumulative dose s of etoposide and bleomycin applied in the two treatment arms were co mparable. Fifty-four patients were entered on the trial, 29 were treat ed with FEB and 25 with CEB chemotherapy. Patients were stratified acc ording to disease extent (minimal versus moderate) and the degree of t umor marker elevation. Thirty-two patients (59%) belonged to the group with minimal disease and low markers. Results: No significant differe nce in response to chemotherapy was seen between the two arms, with CR rates of 81% for the FEB arm and 76% for CEB treatment. However, more patients treated with CEB (32% versus 13%) have relapsed after therap y, and 4 patients (16%) have died of disease progression after CEB in contrast to 1 (3%) after FEB therapy. The first interim analysis of ne gative events (relapse, vital tumor at secondary resection, death from the disease and therapy-associated death) showed a significantly high er rate after CEB than after FEB therapy, and the trial was terminated early. After a median follow-up of 33 months for all patients, the ca lculation of negative events is still significantly in favour of FEB-t reated patients, particularly since three late relapses >2 years have been observed in the CEB arm (P = 0.03). Conclusion: This randomized t rial demonstrates that even with the use of adequate doses of etoposid e and full-dose bleomycin, carboplatin cannot altogether replace cispl atin in patients with testicular cancer. Treatment with the FEB regime n remains the standard approach in patients with 'good-risk' non-semin omatous germ cell tumors.