Hartmann J T, Kuczyk M A, Kollmannsberger C, Kanz L, Bokemeyer C
UKT - University Medical Center II, Department of Hematology/Oncology/Immunology, Eberhard-Karls-University Tübingen, Germany.
World J Urol. 1999 Oct;17(5):324-33. doi: 10.1007/s003450050155.
The current aims of chemotherapy in metastatic testicular cancer are to reduce 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, consisting of cisplatin, etoposide, and bleomycin, remain the standard treatment for good-prognosis patients despite a number of randomized studies trying to avoid the toxicity of bleomycin or to abandon cisplatin-associated side effects by substitution with the less toxic analogue carboplatin. In patients with intermediate- and poor-prognosis criteria, four cycles of PEB given at 3-weekly 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 with poor-prognosis metastatic disease and for patients with relapse after previous chemotherapy. Favorable results with long-term survival rates of approximately 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 patients. A randomized phase III trial comparing conventional dose chemotherapy (4x PEB) with HDCT (2x PEB + 2x HD-CEC) was initiated as a United States intergroup trial in 1996. In patients with relapsed disease, conventional salvage chemotherapy results in only an approximately 20% long-term survival rate. Particularly, primary mediastinal disease and chemotherapy refractoriness represent variables associated with a very poor outcome. HDCT is also employed in relapsed patients to improve the long-term outcome. Long-term toxicity of treatment has become an important issue due to the large group of patients with metastatic disease now being cured with modern treatment strategies. The cumulative dose of cisplatin applied has been identified as a major risk factor for the development of many types of late toxicity. Despite the major advances made in the last 20 years, evaluation of the role of HDCT in both first-line and salvage treatment, investigation of new cytotoxic agents in refractory patients, and assessment of the long-term toxicities are major tasks that remain to be addressed in controlled clinical trials.
转移性睾丸癌化疗目前的目标是，在不影响疗效的情况下，降低“预后良好”的转移性疾病患者的治疗相关毒性，并通过使用更强化疗方案，改善根据国际生殖细胞癌协作组（IGCCCG）分类为“预后不良”患者的治疗效果。尽管有多项随机研究试图避免博来霉素的毒性，或用毒性较小的类似物卡铂替代顺铂以消除其相关副作用，但由顺铂、依托泊苷和博来霉素组成的三个周期的PEB化疗，仍然是预后良好患者的标准治疗方案。对于预后中等和不良标准的患者，每3周进行一次共四个周期的PEB化疗被视为常规治疗。对于最初表现为预后不良的转移性疾病患者以及先前化疗后复发的患者，目前正在研究高剂量化疗联合外周血干细胞（PBSC）移植（HDCT）的作用。在德国睾丸癌研究组（GTCSG）的一项I-II期试验中，前期序贯HDCT已在这类患者中取得了约75%的长期生存率的良好结果。1996年，一项作为美国多中心试验开展的随机III期试验，比较了传统剂量化疗（4×PEB）与HDCT（2×PEB + 2×HD-CEC）。在复发疾病患者中，传统的挽救性化疗长期生存率仅约为20%。特别是，原发性纵隔疾病和化疗难治性是与非常差的预后相关的变量。HDCT也用于复发患者以改善长期预后。由于现在一大批转移性疾病患者通过现代治疗策略得以治愈，治疗的长期毒性已成为一个重要问题。已确定顺铂的累积剂量是发生多种晚期毒性的主要危险因素。尽管在过去20年中取得了重大进展，但评估HDCT在一线和挽救治疗中的作用、研究难治性患者的新型细胞毒性药物以及评估长期毒性，仍是有待在对照临床试验中解决的主要任务。
