High-Dose Chemotherapy in Poor-Risk Germ-Cell Tumors

Testicular cancer has become a model for a curable neoplasm. The results of the treatment of disseminated germ-cell tumors have dramatically improved by utilization of platinum-containing combination chemotherapy regimens. Patients with metastatic disease are allocated to either good-risk or poor-risk groups according to prognostic classifications or models.[1-3] The standard treatment for good-risk patients is three cycles of PEB (Platinol [cisplatin], etoposide, bleomycin [Blenoxane]), with poor-risk patients receiving four cycles. The standard treatment achieves 95% and 65% cure rates in good-risk and poor-risk patients, respectively. However, 10% to 25% of patients in complete remission fail to maintain the remission. The standard second-line treatment is VeIP (Velban [vinblastine], ifosfamide [Ifex], Platinol) or VIP (VePesid [etoposide], ifosfamide, Platinol), which induces a complete response in 60% of patients and a long-term remission in 20% to 30% of patients.[4] Thus, a number of patients may fail to attain complete responses. Durable complete responses have been achieved in only one-third of patients with poor-risk germ-cell tumors (GCT) by Memorial Sloan-Kettering Center (MSKCC) criteria (Table 1). Likewise, one-half of those considered poor risk by Indiana criteria achieve a durable complete response to four cycles of PEB chemotherapy.[5] The use of high-dose chemotherapy with autologous bone marrow transplantation (BMT) and/or peripheral stem-cell transplantation (PSCT) as salvage therapy for relapsed or refractory germ-cell tumors has been explored. The object of this article is to review the various trials employing high-dose chemotherapy. High-dose chemotherapy has been used in two settings: in heavily pretreated patients and in first-salvage or first-line therapy.