High-dose cisplatin and VP-16 with bleomycin, in the management of advanced metastatic germ cell tumors.

Intensive combination chemotherapy consisting of cisplatin 40 mg/m2 daily X 5, VP-16 200 mg/m2 daily X 5 and bleomycin 15 mg/m2 every week was administered to 29 patients (22 previously untreated and seven previously treated) with poor prognosis germ cell tumors. Eighty-six per cent of the previously untreated patients obtained CR and 5% PR. Seventeen patients (77%) are alive without evidence of disease after a median observation time of 11 months (range 1+-19+ months) after treatment. Seventy-one per cent of the previously treated patients obtained CR and 14% PR. Six patients are still alive and four (57%) without evidence of disease after a median observation time of 9 months (range 3+-12+ months) after treatment. Toxicity was severe in both groups. In 73% of the cycles WBC was below 1.0 X 10(9)/1, and in 74% of the cycles thrombocytes was below 25 X 10(9)/1. Ninety-one per cent had at least one incidence with culture negative neutropenic fever, and in four patients bacteremia was documented. Kidney function decreased (median 33%) in previously untreated patients as measured by 51Cr-EDTA clearance. Ototoxicity was observed in around 60% of the patients (two patients has required the use of a hearing aid) and neurotoxicity in around 40%. Neurotoxicity was mild in most cases. The results of the present investigation are encouraging and justify an aggressive therapeutic approach to patients with poor prognosis germ cell tumors. The toxicity is substantial, but manageable, and only a prospective randomized study can substantiate whether this excess in toxicity can be translated into an improved survival and cure.