Randomised phase III trial of adjuvant chemotherapy with oral uracil and tegafur plus leucovorin versus intravenous fluorouracil and levofolinate in patients with stage III colorectal cancer who have undergone Japanese D2/D3 lymph node dissection: Final results of JCOG0205
Randomised phase III trial of adjuvant chemotherapy with oral uracil and tegafur plus leucovorin versus intravenous fluorouracil and levofolinate in patients with stage III colorectal cancer who have undergone Japanese D2/D3 lymph node dissection: Final results of JCOG0205
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DOI：
10.1016/j.ejca.2014.05.025
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发表时间：
2014-09-01
影响因子：
8.4
通讯作者：
Moriya, Yoshihiro
中科院分区：
文献类型：
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作者：
Shimada, Yasuhiro;Hamaguchi, Tetsuya;Moriya, Yoshihiro
工作背景：NSABP C-06证明了口服辅助尿嘧啶和替加氟加亚叶酸（UFT/LV）在II/III期结肠癌无病生存期（DFS）方面非劣效于每周一次氟尿嘧啶和亚叶酸（5-FU/LV）。这是JC 000205的第一份报告，该报告比较了UFT/LV与标准5-FU/左亚叶酸（1-LV）用于接受日本D2/D3淋巴结清扫术的III期结直肠癌患者。患者随机接受3个疗程的5-FU/1-LV治疗（5-FU 500 mg/m2，1-LV 250 mg/m2，第1、8、15、22、29、36天，每8周一次）或5个疗程的UFT/LV（UFT 300 mg m（-2），第-1天，LV 75 mg/天，第1-28天，每5周一次）。主要终点为DFS。样本量为1100，单侧α为0.05，把握度为0.78，风险比的非劣效性界值为1.27。该试验已在UMIN-CTR注册（C 000000193）。结果：2003年2月至2006年11月期间，1，101例患者（1092例合格患者）被随机分配至5-FU/1-LV组（n = 550）或UFT/LV组（n = 551）。中位年龄：61岁，结肠/直肠：67%/33%，阳性淋巴结数量3：73%/27%，IIIa/IIIb期：75%/25%。DFS的风险比为1.02（91.3%置信区间，0.84-1.23），证明UFT/LV的非劣效性（P = 0.0236）。5年总生存率（87.5%）高于NSABP C-06（69.6%）。3/4级毒性分别为5-FU/1-LV组8.4%中性粒细胞减少和UFT/LV组8.7%丙氨酸氨基转移酶升高。两个目标之间腹泻（9.6% vs 8.5%）和厌食（4.0% vs 3.7%）的发生率相似。解释：辅助UFT/LV在DFS方面不劣于标准5-FU/1-LV。UFT/LV应该是接受日本D2/D3淋巴结清扫术的III期结肠癌患者的口服治疗选择。(C)2014爱思唯尔有限公司版权所有。
Background: NSABP C-06 demonstrated the non-inferiority of oral adjuvant uracil and tegafur plus leucovorin (UFT/LV) to weekly fluorouracil and folinate (5-FU/LV) with respect to disease-free survival (DFS) for stage II/III colon cancer. This is the first report of JC000205, which compared UFT/LV to standard 5-FU/levofolinate (1-LV) for stage III colorectal cancer patients who have undergone Japanese D2/D3 lymph node dissection.Methods: Patients were randomised to three courses of 5-FU/1-LV (5-FU 500 mg/m(2), 1-LV 250 mg/m(2) on days 1, 8, 15, 22, 29, 36 every 8 weeks) or five courses of UFT/LV (UFT 300 mg m(-2) day-1, LV 75 mg/day on days 1-28 every 5 weeks). The primary end-point was DFS. The sample size was 1100 determined with one-sided alpha of 0.05, power of 0.78 and non-inferiority margin of hazard ratio of 1.27. This trial is registered with UMIN-CTR (C000000193).Findings: Between February 2003 and November 2006, 1,101 patients (1092 eligible patients) were randomised to 5-FU/1-LV (n = 550) or UFT/LV (n = 551). Median age: 61 years, colon/rectum: 67%/33%, number of positive nodes 3: 73%/27%, stage IIIa/IIIb: 75%/25%. The hazard ratio of DFS was 1.02 (91.3% confidence interval, 0.84-1.23), demonstrating the non-inferiority of UFT/LV (P = 0.0236). Five-year overall survival (87.5%) was higher than that in NSABP C-06 (69.6%). Grade 3/4 toxicities were 8.4% neutropenia in 5-FU/1-LV and 8.7% alanine aminotransferase elevation in UFT/LV, respectively. The incidences of diarrhoea (9.6% versus 8.5%) and anorexia (4.0% versus 3.7%) were similar between the two aims. No treatment-related deaths were reported.Interpretation: Adjuvant UFT/LV is non-inferior to standard 5-FU/1-LV with respect to DFS. UFT/LV should be an oral treatment option for patients with stage III colon cancer who have undergone Japanese D2/D3 lymph node dissection. (C) 2014 Elsevier Ltd. All rights Reserved.