Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results from the X-ACT trial with analysis by age and preliminary evidence of a pharmacodynamic marker of efficacy
Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results from the X-ACT trial with analysis by age and preliminary evidence of a pharmacodynamic marker of efficacy
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DOI：
10.1093/annonc/mdr366
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发表时间：
2012-05-01
影响因子：
50.5
通讯作者：
Cassidy, J.
中科院分区：
文献类型：
--
作者：
Twelves, C.;Scheithauer, W.;Cassidy, J.
背景：这项多中心随机试验比较了口服卡培他滨与静脉推注5 - 氟尿嘧啶（5 - FU）/亚叶酸（FA）作为Ⅲ期结肠癌辅助治疗的效果。
患者与方法：患者被分配接受为期24周的治疗，卡培他滨组为每3周的第1 - 14天每天两次，每次1250 mg/m²，或接受5 - FU/FA（梅奥诊所方案）治疗。主要终点是无病生存期（DFS）。
结果：意向性治疗人群接受了卡培他滨（n = 1004）或5 - FU/FA（n = 983）治疗。中位随访6.9年，卡培他滨在DFS[风险比（HR）= 0.88；95%置信区间（CI）0.77 - 1.01]和总生存期（OS）（HR = 0.86；95% CI 0.74 - 1.01）方面至少与5 - FU/FA相当；95% CI上限显著低于预先设定的非劣效性边界1.20（P < 0.0001）和1.14（P < 0.001）。这种情况在所有亚组中均保持一致，包括70岁的患者。预先计划的多变量分析显示，与5 - FU/FA相比，卡培他滨对DFS（P = 0.021）和OS（P = 0.020）具有统计学上显著的有益影响。一项事后分析表明，手足综合征的发生可能与卡培他滨接受者更好的预后相关。
结论：口服卡培他滨是静脉推注5 - FU/FA作为Ⅲ期结肠癌患者辅助治疗的有效替代方案，其疗效优势在5年及老年患者中均得以维持。
Background: This multicenter randomized trial compared oral capecitabine with bolus i.v. 5-fluorouracil (5-FU)/folinic acid (FA) as adjuvant therapy for stage III colon cancer.Patients and methods: Patients were assigned to 24 weeks of capecitabine 1250 mg/m(2) twice daily on days 1-14 every 3 weeks or 5-FU/FA (Mayo Clinic regimen). The primary end point was disease-free survival (DFS).Results: The intent-to-treat population received capecitabine (n = 1004) or 5-FU/FA (n = 983). With a median follow-up of 6.9 years, capecitabine was at least equivalent to 5-FU/FA in terms of DFS [hazard ratio (HR) = 0.88; 95% confidence interval (CI) 0.77-1.01] and overall survival (OS) (HR = 0.86; 95% CI 0.74-1.01); the 95% CI upper limits were significantly less than the predefined noninferiority margins of 1.20 (P < 0.0001) and 1.14 (P < 0.001), respectively. This pattern was maintained in all subgroups, including patients aged 70 years. Preplanned multivariate analyses showed that capecitabine had statistically significant beneficial effects on DFS (P = 0.021) and OS (P = 0.020) versus 5-FU/FA. A post hoc analysis suggested that the occurrence of hand-foot syndrome may be associated with better outcomes in capecitabine recipients.Conclusion: Oral capecitabine is an effective alternative to bolus 5-FU/FA as adjuvant treatment of patients with stage III colon cancer with efficacy benefits maintained at 5 years and in older patients.