Randomized Phase II/III Trial Assessing Gemcitabine/Carboplatin and Methotrexate/Carboplatin/Vinblastine in Patients With Advanced Urothelial Cancer Who Are Unfit for Cisplatin-Based Chemotherapy: EORTC Study 30986
Randomized Phase II/III Trial Assessing Gemcitabine/Carboplatin and Methotrexate/Carboplatin/Vinblastine in Patients With Advanced Urothelial Cancer Who Are Unfit for Cisplatin-Based Chemotherapy: EORTC Study 30986
复制标题
DOI：
10.1200/jco.2011.37.3571
复制
发表时间：
2012-01-10
影响因子：
45.3
通讯作者：
Sylvester, Richard
中科院分区：
文献类型：
--
作者：
De Santis, Maria;Bellmunt, Joaquim;Sylvester, Richard
目的：这是第一个随机II/III期试验，比较两种以卡铂为基础的化疗方案在不适合顺铂化疗的尿路上皮癌患者中的应用。患者和方法本研究III期部分的主要目的是比较可测量疾病和肾功能受损（肾小球滤过率< 60但> 30 mL/min）和/或表现评分为2的化疗初治患者的总生存期（OS），这些患者被随机分配接受吉西他滨/卡铂（GC）或甲氨蝶呤/卡铂/长春花碱（M-CAVI）。为了检测与M-CAVI相比，GC的中位生存期增加了50% （13.5 v 9个月），基于双侧log-rank检验，错误率为alpha = 0.05和beta = 0.20，需要225例患者。次要终点是总缓解率（ORR）、无进展生存期（PFS）、毒性和生活质量。结果238例患者从29家医院随机抽取，随访7年。中位随访时间为4.5年。胃癌患者的最佳orr为41.2%（36.1%确认缓解），而M-CAVI患者的最佳orr为30.3%（21.0%确认缓解）（P = 0.08）。GC组中位OS为9.3个月，M-CAVI组中位OS为8.1个月（P = 0.64）。两组间PFS无差异（P = 0.78）。在9.3%的GC患者和21.2%的M-CAVI患者中观察到严重的急性毒性（死亡、4级血小板减少并出血、3级或4级肾毒性、中性粒细胞减少症发烧或粘膜炎）。结论两组间疗效无显著差异。M-CAVI组的严重急性毒性发生率较高。[J]中华临床杂志，30(3):391 - 391。(C) 2011年美国临床肿瘤学会
PurposeThis is the first randomized phase II/III trial comparing two carboplatin-based chemotherapy regimens in patients with urothelial cancer who are ineligible ("unfit") for cisplatin chemotherapy.Patients and MethodsThe primary objective of the phase III part of this study was to compare the overall survival (OS) of chemotherapy-naive patients with measurable disease and an impaired renal function (glomerular filtration rate < 60 but > 30 mL/min) and/or performance score of 2 who were randomly assigned to receive either gemcitabine/carboplatin (GC) or methotrexate/carboplatin/vinblastine (M-CAVI). To detect an increase of 50% in median survival with GC compared with M-CAVI (13.5 v 9 months) based on a two-sided log-rank test at error rates alpha = .05 and beta = .20, 225 patients were required. Secondary end points were overall response rate (ORR), progression-free survival (PFS), toxicity, and quality of life.ResultsIn all, 238 patients were randomly assigned by 29 institutions over a period of 7 years. The median follow-up was 4.5 years. Best ORRs were 41.2% (36.1% confirmed response) for patients receiving GC versus 30.3% (21.0% confirmed response) for patients receiving M-CAVI (P = .08). Median OS was 9.3 months in the GC arm and 8.1 months in the M-CAVI arm (P = .64). There was no difference in PFS (P = .78) between the two arms. Severe acute toxicity (death, grade 4 thrombocytopenia with bleeding, grade 3 or 4 renal toxicity, neutropenic fever, or mucositis) was observed in 9.3% of patients receiving GC and 21.2% of patients receiving M-CAVI.ConclusionThere were no significant differences in efficacy between the two treatment groups. The incidence of severe acute toxicities was higher for those receiving M-CAVI. J Clin Oncol 30:191-199. (C) 2011 by American Society of Clinical Oncology