High-dose chemotherapy for resistant germ cell tumors: recent advances and future directions

A review of the published literature shows that treatment with high-dose carboplatin and etoposide with autologous bone marrow transplantation results in durable complete responses (3-42 months, continuous at time of report) in about 10%-20% of heavily pretreated patients with cisplatin-resistant germ cell tumors and represents a curative therapy in patients who would otherwise die of their disease. In a recent follow-up study of 40 patients with refractory germ cell tumors, 15% (six) were alive and free of disease more than 24 months after treatment with high-dose carboplatin and etoposide with autologous bone marrow transplantation. The several studies that incorporated an oxazaphosphorine (usually cyclophosphamide) in the regimen strongly suggest that the addition of this third drug to high doses of carboplatin and etoposide results in a higher proportion of complete responses (35%, 23% durable) than carboplatin and etoposide alone (26%, 12% durable). Early intervention with high-dose chemotherapy and autologous bone marrow transplantation appears to reduce hematologic toxicity. Its role in the treatment of less heavily pretreated patients will depend on the definition of "cisplatin-resistant," which may encompass those who failed to respond to the drug or those who are judged not likely to respond. Studies to improve treatment efficacy and to lessen the burden of supportive care during hematopoietic reconstitution are ongoing and include the use of peripheral blood-derived stem cells.