Multicenter phase III study of uracil/tegafur and oral leucovorin versus fluorouracil and leucovorin in patients with previously untreated metastatic colorectal cancer
Multicenter phase III study of uracil/tegafur and oral leucovorin versus fluorouracil and leucovorin in patients with previously untreated metastatic colorectal cancer
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DOI：
10.1200/jco.2002.04.123
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发表时间：
2002-09-01
影响因子：
45.3
通讯作者：
Benner, SE
中科院分区：
文献类型：
--
作者：
Douillard, JY;Hoff, PM;Benner, SE
目的：这项III期研究旨在证明口服尿嘧啶/替加氟（UFT）和口服亚叶酸（LV）与传统静脉注射（IV）氟尿嘧啶（5-FU）和IV在既往未经治疗的转移性结直肠癌中的生存率等效。患者和方法：816例患者随机接受UFT治疗，（300 mg/m2/d）和LV（75或90 mg/d），持续28天，每35天一次或IV推注5-FU结果：UFT/LV方案与IV 5-FU/LV方案的生存率相当。UFT/LV组的中位生存期为12.4个月（95%置信区间[CI]，11.2 - 13.6个月），5-FU/LV组为13.4个月（95% CI，11.6 - 15.4个月）（P = 0.630）。生存风险比为0.964（95.6% CI，0.826 - 1.125），支持等效生存。治疗组间的总体缓解率无差异（UFT/LV，11.79%; 5-FU/LV，14.5%; P = 0.232）。中位至进展时间支持5-FU/LV（UFT/LV，3.5个月; 5-FU/LV，3.8个月; P = 0.011），但两组之间的肿瘤评估时间表不同。与5-FU/LV相比，UFT/LV显著改善了安全性。UFT/LV组腹泻、恶心和呕吐、口腔炎和粘膜炎的发生率显着降低，骨髓抑制也是如此。接受UFTAV治疗的患者较少发生发热性中性粒细胞减少（P
Purpose: This phase III study was designed to demonstrate equivalence in survival of oral uracil/tegafur (UFT) and oral leucovorin (LV) to conventional intravenous (IV) fluorouracil (5-FU) and IV in previously untreated metastatic colorectal carcinoma. Safety was also compared.Patients and Methods: Eight hundred sixteen patients were randomized to receive either UFT (300 mg/m(2)/d) and LV (75 or 90 mg/d) for 28 days every 35 days or IV bolus 5-FU (425 mg/m(2)/d) and IV (20 mg/m(2)/d) for 5 days every 28 days.Results: UFT/LV produced survival comparable to the IV 5-FU/LV regimen. Median survival was 12.4 months (95% confidence interval [CI], 11.2 to 13.6 months) with UFT/LV and 13.4 months (95% CI, 11.6 to 15.4 months) with 5-FU/LV (P =.630). The hazard ratio for survival was 0.964 (95.6% CI, 0.826 to 1.125), supporting equivalent survival. The overall response rate did not differ between treatment arms (UFT/LV, 11.79%; 5-FU/LV, 14.5%; P =.232). Median time to progression favored 5-FU/LV (UFT/LV, 3.5 months; 5-FU/LV, 3.8 months; P =.011), but tumor assessment schedules differed between arms. UFT/LV significantly improved safety compared with 5-FU/LV. Diarrhea, nausea and vomiting, and stomatitis and mucositis were significantly less frequent with UFT/LV, as was myelosuppression. Patients treated with UFTAV had fewer episodes of febrile neutropenia (P