HIGH-DOSE CHEMOTHERAPY IN GERM-CELL TUMORS

The majority of patients with advanced-stage germ-cell tumor are curab le by cisplatin-based chemotherapy, but about 10% of those in the good -risk and 30%-50% in the poor-risk groups will experience relapse. Pat ients 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 b een developed specifically for this patient population: they are usual ly based on combinations of etoposide, cyclophosphamide, ifosfamide an d, originally, double-dose cisplatin or, nowadays, high-dose carboplat in. The role of high-dose chemotherapy was studied initially in salvag e 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 longterm complete remissions. Prognostic fact ors for outcome were disease status (absolute refractory, refractory o r sensitive diseases), primary tumor site, response to prior chemother apy and serum hCG levels prior to high-dose treatment. Patients with n o adverse prognostic factors have a greater than 50% chance of cure af ter high-dose treatment. Patients with refractory disease did not bene fit from high-dose chemotherapy. A randomized European trial is ongoin g to evaluate prospectively the role of high-dose chemotherapy in comp arison to standard ifosfamide-based salvage treatment. In first-line c onsolidation treatment of poor-risk nonseminomatous germ-cell tumors, the results of phase II trials with carboplatin-based high-dose therap y are in favor of a survival impact when compared to historical contro ls. A prospective randomized trial is ongoing in the US to study the r ole of carboplatin-based high-dose consolidation treatment. The only p rospective trial comparing a cisplatin-based high-dose treatment to st andard chemotherapy failed to demonstrate any survival advantage for t he high-dose procedure in this setting. New developments include the u se of repeated cycles of high-dose chemotherapy with peripheral blood stem-cell support and the introduction of paclitaxel, a new active dru g in this disease, and other non-cross-resistant cytotoxic agents in h igh-dose combination regimens.