High-dose chemotherapy in germ-cell tumors

Abstract

The majority of patients with advanced-stage germ-cell tumor are curable by cisplatin-based chemotherapy, but about 10% of those in the good-risk and 30%-50% in the poor-risk groups will experience relapse. Patients in first relapse have a 60% chance of entering a second complete remission and a 15%-25% probability that it will be durable. Regimens of high-dose chemotherapy with hematopoietic stem-cell support have been developed specifically for this patient population: they are usually based on combinations of etoposide, cyclophosphamide, ifosfamide and, originally, double-dose cisplatin or, nowadays, high-dose carboplatin. The role of high-dose chemotherapy was studied initially in salvage and later in first-line treatment. Four hundred thirty six patients who received high-dose salvage chemotherapy have been reported, 96 (22%) of whom have obtained long-term complete remissions. Prognostic factors for outcome were disease status (absolute refractory, refractory or sensitive diseases), primary tumor site, response to prior chemotherapy and serum hCG levels prior to high-dose treatment. Patients with no adverse prognostic factors have a greater than 50% chance of cure after high-dose treatment. Patients with refractory disease did not benefit from high-dose chemotherapy. A randomized European trial is ongoing to evaluate prospectively the role of high-dose chemotherapy in comparison to standard ifosfamide-based salvage treatment. In first-line consolidation treatment of poor-risk nonseminomatous germ-cell tumors, the results of phase II trials with carboplatin-based high-dose therapy are in favor of a survival impact when compared to historical controls. A prospective randomized trial is ongoing in the US to study the role of carboplatin-based high-dose consolidation treatment. The only prospective trial comparing a cisplatin-based high-dose treatment to standard chemotherapy failed to demonstrate any survival advantage for the high-dose procedure in this setting. New developments include the use of repeated cycles of high-dose chemotherapy with peripheral blood stem-cell support and the introduction of paclitaxel, a new active drug in this disease, and other non-cross-resistant cytotoxic agents in high-dose combination regimens.