Twelve patients with refractory germ cell tumors were treated with etoposide (VP16) (100 g/m2/day X 5) and very high dose cisplatin (VHD-CDDP) (40 mg/m2/day X 5) every 28 days. All patients had progressed or relapsed after therapy with vinblastine (0.15 mg/kg/day X 2), CDDP (20 mg/m2/day X 5), and bleomycin (30 units/week). Thirty-three cycles of VP16 plus VHD-CDDP were administered. Five patients achieved complete response (two with chemotherapy only, two with chemotherapy + surgery, and one with chemotherapy + irradiation), five achieved partial response (two continue therapy), and two had disease progression. Only one patient achieved prolonged complete response (24+ months). Myelosuppression (median wbc count nadir, 1200/mm3; median platelet count nadir, 18,500/mm3), neurotoxicity (five patients with diminished hearing and six with substantial peripheral neuropathy), and hypomagnesemia (21 of 22 courses; magnesium, less than 1.5 mg/dl) were the dominant toxic effects. No important nephrotoxicity was seen (median maximum creatinine, 1.2 mg/dl; range, 0.8-2.2). VP16 plus VHD-CDDP is safe and tolerable and may provide a non-cross-resistant alternative to vinblastine, CDDP, and bleomycin.
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