Comparison of two standard chemotherapy regimens for good-prognosis germ-cell tumours: a randomised trial
Comparison of two standard chemotherapy regimens for good-prognosis germ-cell tumours: a randomised trial
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DOI：
10.1016/s0140-6736(00)04165-9
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发表时间：
2001-03-10
期刊：
影响因子：
168.9
通讯作者：
Simes, RJ
中科院分区：
文献类型：
--
作者：
Toner, GC;Stockler, MR;Simes, RJ
背景：大多数转移性生殖细胞肿瘤患者可通过化疗治愈。然而，最优的化疗方案尚不确定，国际上的做法也存在差异。我们进行了一项多中心随机试验，比较两种标准化疗方案对预后良好的男性生殖细胞肿瘤的疗效。第一个方案(方案A)基于印第安纳大学的治疗建议，包括三个周期，顺铂20 mg/m(2)，第1~5天；依托泊苷100 mg/m(2)，第1~5天；博莱霉素30ku，第1、8、15天，每21天重复一次。第二个方案(方案B)以已发表的随机临床试验的对照方案为基础，包括四个周期，顺铂100 mg/m(2)，第1天；依托泊苷120 mg/m(2)，第1天；博莱霉素30ku，第1天，每21天重复。主要的结果衡量标准是总体存活率。分析是根据治疗意图进行的。结果166名患者被随机分配，每个方案83人。当第二次计划的中期分析满足预定的停止规则时，试验停止。中位随访期为33个月，A方案的总存活率显著高于A方案(3例死亡，13例死亡，危险比0.22[95%可信区间0.06-0.77]，p=0.008)。这一差异是由于癌症死亡(9例)，而不是治疗死亡(2例)，在调整了其他预后因素后仍然显著(0.25[0.07-0.88]，p=0.03)。印第安纳大学开发的方案在预后良好的男性生殖细胞肿瘤中的解释优于本次试验中研究的替代方案。B方案中博莱霉素的总剂量和剂量强度较低以及依托泊苷的剂量强度较低可能是导致预后较差的原因。
Background Most patients with metastatic germ-cell tumours are cured with chemotherapy. However, the optimum chemotherapy regimen is uncertain, and there is variation in international practice. We did a multicentre randomised trial to compare two standard chemotherapy regimens for men with good-prognosis germ-cell tumours.Methods Good prognosis was defined by modified Memorial Sloan-Kettering criteria. The first regimen (regimen A) was based on treatment recommendations from Indiana University and comprised three cycles of 20 mg/m(2) cisplatin on days 1-5, 100 mg/m(2) etoposide on days 1-5, and 30 kU bleomycin on days 1, 8, and 15, repeated every 21 days. The second regimen (regimen B) was based on the control regimen of a published randomised clinical trial and comprised four cycles of 100 mg/m(2) cisplatin on day 1, 120 mg/m(2) etoposide on days 1-3, and 30 kU bleomycin on day 1, repeated every 21 days. The primary outcome measure was overall survival. Analysis was by intention to treat.Findings 166 patients were randomised, 83 to each regimen. The trial was stopped when the second planned interim analysis met predefined stopping rules. The median follow-up was 33 months, Overall survival was substantially better with regimen A (three vs 13 deaths, hazard ratio 0.22 [95% CI 0.06-0.77], p=0.008). This difference was due to deaths from cancer tone vs nine), and not deaths from treatment (two vs two) and remained significant after adjustment for other prognostic factors (0.25 [0.07-0.88], p=0.03).Interpretation In men with good-prognosis germ-cell tumours, the regimen developed at Indiana University is superior to the alternative regimen studied in this trial. The lower total dose and dose-intensity of bleomycin and the lower dose-intensity of etoposide in regimen B could be responsible for the worse outcome.