Germ cell tumor clinical trials in North America

The management of germ cell tumors (GCT) in men has been the focus of intense clinical investigation over the past 25 years. Following clinical trials which demonstrated that GCTs are curable, considerable effort has been directed at refinement of the multidisciplinary treatment plan. During the past decade, there has been a major emphasis on identifying those clinical prognostic features most closely associated with a high likelihood of a complete response (good risk) and a low likelihood of complete response (poor risk). Randomized good- and poor-risk clinical trials have been conducted which clarify the role of bleomycin and the number of cycles of therapy in good-risk patients and the role of high-dose cisplatin (200 mg/m(2)/cycle) and ifosfamide in poor-risk patients. The efficacy of high-dose chemotherapy with stem cell rescue has led to a randomized trial of its use following standard induction therapy as compared to standard induction therapy in previously untreated poor-risk patients. Salvage chemotherapy for patients in first or second relapse, or those who have not achieved an initial complete response, initially tested the role of ifosfamide; efforts are now focused on the role of paclitaxel and high-dose therapy in specific patient subgroups. High-dose chemotherapy with stem cell rescue is the treatment of choice for patients in second relapse with gonadal primary tumors who have responsive disease and factors which predict a reasonable likelihood of achieving a disease-free status. A general understanding of tumor biology and specific knowledge regarding GCTs will be very important in the next decade of discovery as the pathways of malignant transformation, progression, and drug resistance become better known and serve as targets for new therapy.