Future prospects in the chemotherapy of metastatic nonseminomatous testicular germ-cell cancer

The current aims of chemotherapy in metastatic testicular cancer are to red uce treatment-related toxicity in patients with "good-prognosis" metastatic disease without compromising the efficacy and to improve treatment results in "poor-prognosis" patients according to the IGCCCG classification by the use of more dose-intensive regimens. Three cycles of PEB chemotherapy, con sisting of cisplatin, etoposide, and bleomycin, remain the standard treatme nt for good-prognosis patients despite a number of randomized studies tryin g to avoid the toxicity of bleomycin or to abandon cisplatin-associated sid e effects by substitution with the less toxic analogue carboplatin. In pati ents with intermediate- and poor-prognosis criteria, four cycles of FEB giv en at 3-weekIy intervals are considered routine treatment. The role of high -dose chemotherapy with peripheral blood stem-cell (PBSC) transplantation ( HDCT) is currently being investigated for patients who initially present wi th poor-prognosis metastatic disease and for patients with relapse after pr evious chemotherapy. Favorable results with long-term survival rates of app roximately 75% have been achieved with up-front sequential HDCT in a phase I-II trial of the German Testicular Cancer Study Group (GTCSG) in such pati ents. A randomized phase III trial comparing conventional dose chemotherapy (4xPEB) with HDCT (2xPEB + 2x HD-CEC) was initiated as a United States int ergroup trial in 1996, In patients with relapsed disease, conventional salv age chemotherapy results in only an approximately 20% long-term survival ra te. particularly, primary mediastinal disease and chemotherapy refractorine ss represent variables associated with a very poor outcome. HDCT is also em ployed in relapsed patients to improve the long-term outcome. Long-term tox icity of treatment has become an important issue due to the large group of patients with metastatic disease now being cured with modern treatment stra tegies. The cumulative dose of cisplatin applied has been identified as a m ajor risk factor for the development of many types of late toxicity. Despit e the major advances made in the last 20 years, evaluation of the role of H DCT in both first-line and salvage treatment, investigation of new cytotoxi c agents in refractory patients, and assessment of the long-term toxicities are major tasks that remain to be addressed in controlled clinical trials.