Chemotherapy of disseminated germ cell tumors

The treatment of patients with germ cell neoplasms has improved dramatically during the last 10 years. Combination chemotherapy with cisplatin + vinblastine + bleomycin (PVB) was initiated at Indiana University in 1974. In this original study 28 of 47 patients (60%) with disseminated testicular tumors are currently alive, with a minimal follow-up of 10 years. Our next PVB study demonstrated that the vinblastine dosage could be reduced 25% (0.4 mg/kg to 0.3 mg/kg), thereby significantly reducing toxicity, without compromising the cure rate. Our third generation study confirmed the fact that maintenance therapy was not necessary, and that optimal cure rates could be achieved with merely 12 weeks of PVB induction. Overall, with follow-up of 5 to 10 years, 202 of 272 patients (74%) with disseminated testicular cancer currently are alive on these three PVB protocols. Because of the success of salvage chemotherapy, demonstrating that approximately 25% of patients not curable by PVB achieved durable complete remissions (CRs) with cisplatin + VP-16 combination chemotherapy, our next study compared PVB to cisplatin + VP-16 + bleomycin (PVP16B) as initial chemotherapy for disseminated testicular cancer. This study demonstrated that the two induction regimens produced equivalent CR rates, but that PVP16B was the preferable induction regimen because of a statistically significant reduction in neuromuscular toxicity. Our current studies will evaluate whether three courses (9 weeks) of PVP16B compared to the standard four courses of PVP16B (12 weeks) will achieve similar cure rates in minimal moderate disseminated disease. In advanced disease presentations, we are comparing standard PVP16B to double-dose cisplatin (40 mg/M2 X 5) + VP-16 + bleomycin.