Phase III Randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors
Phase III Randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors
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DOI：
10.1200/jco.2005.05.4528
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发表时间：
2007-01-20
影响因子：
45.3
通讯作者：
Bosl, George J.
中科院分区：
文献类型：
--
作者：
Motzer, Robert J.;Nichols, Craig J.;Bosl, George J.
目的探讨大剂量化疗（HDCT）作为一线治疗对转移性生殖细胞肿瘤（GCT）和预后不良的临床特征的作用。前瞻性评估化疗期间血清肿瘤标志物下降作为治疗outcome.Patients和方法的预测指标。在这项随机III期试验中，既往未经治疗的中度或低风险GCT患者接受标准博莱霉素、依托泊苷和顺铂治疗4个周期（单独的BEP），或两个周期的BEP，接着两个周期的含卡铂的HDCT，然后通过造血干细胞拯救（BEP + HDCT）。血清肿瘤标志物甲胎蛋白和人绒毛膜促性腺激素与治疗结果作为次要终点。结果219例患者被随机分配：108例BEP + HDCT和111例BEP单独。BEP + HDCT治疗组的1年持续完全缓解率为52%，单用BEP治疗组为48%（P +0.53）。在前两个化疗周期中血清肿瘤标志物（甲胎蛋白和/或人绒毛膜促性腺激素）下降缓慢的患者与标志物下降满意的患者相比，无进展生存期和总生存期较短（分别为P +0.02和P = 0.03）。在67例标志物下降不满意的患者中，接受HDCT的患者1年持续完全缓解比例为61%，而接受BEP的患者仅为34%（P = .03）。结论常规纳入HDCT作为GCT转移患者的一线治疗，化疗预测结果不佳，并没有改善治疗结果。在BEP化疗的前两个周期中，频繁测定血清标志物以估计标志物下降，可提供临床有用的结局估计。
Purpose To investigate the role of high-dose chemotherapy (HDCT) as first-line treatment in patients with metastatic germ cell tumor (GCT) and poor-prognostic clinical features. Serum tumor marker decline during chemotherapy was assessed prospectively as a predictor of treatment outcome.Patients and Methods In this randomized phase III trial, previously untreated patients with intermediate- or poor-risk GCT received either four cycles of standard bleomycin, etoposide, and cisplatin (BEP alone), or two cycles of BEP followed by two cycles of HDCT containing carboplatin and then by hematopoietic stem-cell rescue (BEP + HDCT). Serum tumor markers alpha-fetoprotein and human chorionic gonadotrophin were correlated with treatment outcome as a secondary end point.Results Two hundred nineteen patients were randomly assigned: 108 to BEP + HDCT and 111 to BEP alone. The 1-year durable complete response rate was 52% after BEP + HDCT and 48% after BEP alone ( P + .53). Patients with slow serum tumor marker decline (alpha-fetoprotein and/or human chorionic gonadotrophin) during the first two cycles of chemotherapy had a shorter progression-free survival and overall survival compared with patients with satisfactory marker decline ( P + .02 and P = .03, respectively). Among 67 patients with unsatisfactory marker decline, the 1-year durable complete response proportion was 61% for patients who received HDCT versus 34% for patients receiving BEP alone ( P = .03).Conclusion The routine inclusion of HDCT in first-line treatment for GCT patients with metastases and a poor predicted outcome to chemotherapy did not improve treatment outcome. Frequent serum marker determinations to estimate marker decline during the first two cycles of BEP chemotherapy provide a clinically useful estimate of outcome.