Effect of adjuvant capecitabine or fluorouracil, with or without oxaliplatin, on survival outcomes in stage III colon cancer and the effect of oxaliplatin on post-relapse survival: a pooled analysis of individual patient data from four randomised controlled trials.
Effect of adjuvant capecitabine or fluorouracil, with or without oxaliplatin, on survival outcomes in stage III colon cancer and the effect of oxaliplatin on post-relapse survival: a pooled analysis of individual patient data from four randomised controlled trials.
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DOI：
10.1016/s1470-2045(14)70486-3
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发表时间：
2014-12
期刊：
影响因子：
--
通讯作者：
Haller D
中科院分区：
文献类型：
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作者：
Schmoll HJ;Twelves C;Sun W;O'Connell MJ;Cartwright T;McKenna E;Saif M;Lee S;Yothers G;Haller D
基于奥沙利铂的辅助治疗是 III 期结肠癌的标准治疗。尚未直接比较含或不含奥沙利铂的辅助卡培他滨与含或不含奥沙利铂的亚叶酸和氟尿嘧啶；因此，我们的目的是使用四项随机对照试验汇总的个体患者数据来分析这些治疗的有效性和安全性。我们还评估了复发后生存率，据推测接受奥沙利铂辅助治疗的患者的生存率更差。对来自四项随机对照试验（NSABP C-08、XELOXA、X-ACT 和 AVANT；总共 8734 名患者）的年龄为 18 岁或以上、东部肿瘤合作组表现状态为 0 或 1 的已切除 III 期结肠癌患者进行了汇总和分析。我们分析中包括的治疗方案是： XELOX（奥沙利铂和卡培他滨）；亚叶酸和氟尿嘧啶；卡培他滨； FOLFOX-4（亚叶酸、氟尿嘧啶和奥沙利铂）；和改良的 FOLFOX-6 (mFOLFOX-6)。无病生存期是为该分析提供患者的所有试验的主要终点。在这里，我们比较了接受卡培他滨联合或不联合奥沙利铂的患者组与接受亚叶酸和氟尿嘧啶联合或不联合奥沙利铂的患者组之间的无病、无复发和总生存率。比较 XELOX 和 FOLFOX 组合组以及亚叶酸和氟尿嘧啶组之间的复发后生存率。还比较了卡培他滨联合或不联合奥沙利铂组与亚叶酸和氟尿嘧啶联合或不联合奥沙利铂组之间的复发后生存率。在调整分析（风险比 [HR] 1·02 [0·93–1·11；p=0·72]）或未调整分析（HR 1·01 [95% CI 0·92–1·10；p=0·86]）中，接受亚叶酸和氟尿嘧啶治疗的患者与接受卡培他滨治疗的患者之间的无病生存期没有显着差异。无复发生存期相似（调整后的 HR 1·02 [0·93–1·12；p=0·72] 和未调整的 HR 1·01 [95% CI 0·92–1·11；p=0·86]），总生存期也相似（调整后的 HR 1·04 [95% CI 0·93–1·15；p=0·50] 和未调整的 HR 1·02 [0·92–1·14]；p=0·65)。对于总生存期，多重 Cox 回归分析记录了奥沙利铂和氟嘧啶之间的显着相互作用 (p=0·014)。在 XELOX 或 FOLFOX 与亚叶酸和氟尿嘧啶比较的调整分析 (p=0·23) 和未调整分析 (p=0·33) 中，复发后生存率相似，基于卡培他滨的方案与基于亚叶酸和氟尿嘧啶的方案的复发后生存率也相似（未调整 p=0·26）。在 III 期结肠癌的辅助治疗中，与奥沙利铂的联合治疗提供了持续改善的结果，而不会对复发后生存产生不利影响，无论氟嘧啶主链是卡培他滨还是亚叶酸和氟尿嘧啶。这些数据补充了奥沙利铂加卡培他滨或亚叶酸和氟尿嘧啶是 III 期结肠癌辅助治疗的标准治疗的现有证据，并为医生提供了根据患者整体身体表现和偏好灵活治疗患者的机会。基因泰克公司
Oxaliplatin-based adjuvant therapy is the standard of care for stage III colon cancer. Adjuvant capecitabine with or without oxaliplatin versus leucovorin and fluorouracil with or without oxaliplatin has not been directly compared; therefore, we aimed to analyse the efficacy and safety of these treatments using individual patient data pooled from four randomised controlled trials. We also assessed post-relapse survival, which has been postulated to be worse in patients receiving adjuvant oxaliplatin. Patients with resected stage III colon cancer who were 18 years of age or older, with an Eastern Cooperative Oncology Group performance status of 0 or 1, from four randomised controlled trials (NSABP C-08, XELOXA, X-ACT, and AVANT; 8734 patients in total) were pooled and analysed. The treatment regimens included in our analyses were: XELOX (oxaliplatin and capecitabine); leucovorin and fluorouracil; capecitabine; FOLFOX-4 (leucovorin, fluorouracil, and oxaliplatin); and modified FOLFOX-6 (mFOLFOX-6). Disease-free survival was the primary endpoint for all trials that supplied patients for this analysis. Here, we compared disease-free, relapse-free, and overall survival between the patient groups who received capecitabine with or without oxaliplatin and those who received leucovorin and fluorouracil with or without oxaliplatin. Post-relapse survival was compared between the combined XELOX and FOLFOX groups, and the leucovorin and fluorouracil groups. Post-relapse survival was also compared between the capecitabine with or without oxaliplatin and leucovorin and fluorouracil with or without oxaliplatin groups. Disease-free survival did not differ significantly between patients who received leucovorin and fluorouracil versus those who received capecitabine in adjusted analyses (hazard ratio [HR] 1·02 [0·93–1·11; p=0·72]) or in unadjusted analyses (HR 1·01 [95% CI 0·92–1·10; p=0·86]). Relapse-free survival was similar (adjusted HR 1·02 [0·93–1·12; p=0·72] and unadjusted HR 1·01 [95% CI 0·92–1·11; p=0·86]), as was overall survival (adjusted HR 1·04 [95% CI 0·93–1·15; p=0·50] and unadjusted HR 1·02 [0·92–1·14]; p=0·65). For overall survival, a significant interaction between oxaliplatin and fluoropyrimidine was recorded in the multiple Cox regression analysis (p=0·014). Post-relapse survival was similar in adjusted (p=0·23) and unadjusted analyses (p=0·33) for the comparison of XELOX or FOLFOX versus leucovorin and fluorouracil, and was also similar for capecitabine-based regimens versus leucovorin and fluorouracil-based regimens (unadjusted p=0·26). Combination therapy with oxaliplatin provided consistently improved outcomes without adversely affecting post-relapse survival in the adjuvant treatment of stage III colon cancer, irrespective of whether the fluoropyrimidine backbone was capecitabine or leucovorin and fluorouracil. These data add to the existing evidence that oxaliplatin plus capecitabine or leucovorin and fluorouracil is the standard of care for the adjuvant treatment of stage III colon cancer, and offers physicians flexibility to treat patients according to the patients' overall physical performance and preference. Genentech Inc.