Treatment of testicular cancer: a new and improved model

Abstract

Testicular cancer has become a model for a curable neoplasm. Prior to the advent of cisplatin combination chemotherapy, standard chemotherapy consisted of dactinomycin, alone or in combination with chlorambucil and methotrexate. Disseminated germ cell tumors were chemosensitive to these older regimens, with a 50% objective response rate and a 10% to 20% complete remission rate; however, the cure rate was only 5% to 10%. In 1974, we began our initial cisplatin plus vinblastine plus bleomycin (PVB) chemotherapy. Thirty-three of 47 patients with disseminated germ cell tumors treated from 1974 to 1976 achieved a complete remission (CR), and an additional five (11%) were rendered disease-free with post-PVB resection of teratoma or carcinoma. Twenty-seven (57%) of these patients are continuously disease-free with a minimal follow-up of 13 + years. Thus, cisplatin-based chemotherapy produced a one-log increase in the cure rate compared with dactinomycin. A subsequent phase III study performed from 1976 to 1978 demonstrated that the vinblastine dosage could be reduced 25% from 0.4 mg/kg to 0.3 mg/kg with a reduction in toxicity but without any decrement in therapeutic efficacy. A third-generation PVB study from 1978 to 1981 documented that optimal cure rates were achieved with 12 weeks of induction therapy with PVB and that long-term maintenance therapy with vinblastine was unnecessary. In 1978, we initiated salvage therapy with cisplatin plus etoposide (VP-16) in patients not cured with PVB, and 25% of these patients were subsequently cured with this regimen. This represented the first time an adult solid tumor had been cured with a second-line regimen. In 1983, we began studies with third-line therapy with cisplatin plus ifosfamide combination chemotherapy, and even in this refractory setting, approximately 20% of patients are curable. From 1981 to 1984, we compared cisplatin plus VP-16 plus bleomycin (PVP16B) with PVB as first-line chemotherapy. There was a significant reduction in neuromuscular toxicity favoring the VP-16 arm, and furthermore, 78% of these patients were continuously disease-free compared with 66% with PVB. Approximately 75% of patients with disseminated germ cell tumors will be cured with PVP16B, and an additional 10% are curable with salvage chemotherapy. This represents the highest cure rate in any adult malignancy.