BACKGROUND Since 2004, adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX or FLOX) have been the standard of care for patients with resected colon cancer. Herein we examine the change of outcomes over a 10-year period in patients with stage III colon cancer who received this regimen. PATIENTS AND METHODS Individual patient data from the ACCENT database was used to compare the outcomes in older (1998-2003) and newer (2004-2009) treatment eras for patients with stage III colon cancer who received adjuvant FOLFOX or FLOX. The outcomes were compared between the two groups by the multivariate Cox proportional-hazards model adjusting for age, sex, performance score, T stage, N stage, tumor sidedness, and histological grade. RESULTS A total of 6501 patients with stage III colon cancer who received adjuvant FOLFOX or FLOX in six randomized trials were included in the analysis. Patients enrolled in the new era group experienced statistically significant improvement in time to recurrence [3-year rate, 76.1% versus 73.0%; adjusted hazard ratio (HRadj) = 0.83 (95% CI, 0.74-0.92), P = 0.0008], disease-free survival (DFS) [3-year rate, 74.7% versus 72.3%; HRadj = 0.88 (0.79-0.98), P = 0.024], survival after recurrence (SAR) [median time, 27.0 versus 17.7 months; HRadj = 0.65 (0.57-0.74), P < 0.0001], and overall survival (OS) [5-year rate, 80.9% versus 75.7%; HRadj = 0.78 (0.69-0.88), P < 0.0001]. The improved outcomes remained in patients diagnosed at 45 years of age or older, low-risk patients (T1-3 and N1), left colon, mismatch repair proficient (pMMR), BRAF, and KRAS wild-type tumors. CONCLUSION Improved outcomes were observed in patients with stage III colon cancer enrolled in clinical trials who received adjuvant FOLFOX/FLOX therapy in 2004 or later compared with patients in the older era. Prolonged SAR calls for revalidation of 3-year DFS as the surrogate endpoint of OS in adjuvant clinical trials and reevaluation of optimal follow-up of OS to confirm the trial findings based on the DFS endpoints. CLINICAL TRIALS NUMBERS NCT00079274; NCT00096278; NCT00004931; NCT00275210; NCT00265811; NCT00112918.

中文翻译：

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评估 III 期结肠癌患者 10 年期间的结果变化：对 ACCENT 数据库中 6501 名接受氟尿嘧啶、亚叶酸和奥沙利铂治疗的患者进行汇总分析。


背景 自 2004 年以来，5-氟尿嘧啶、亚叶酸和奥沙利铂（FOLFOX 或 FLOX）辅助治疗已成为结肠癌切除患者的标准治疗方法。在此，我们研究了接受该方案的 III 期结肠癌患者 10 年来结果的变化。患者和方法 来自 ACCENT 数据库的个体患者数据用于比较接受 FOLFOX 或 FLOX 辅助治疗的 III 期结肠癌患者在较早治疗时期（1998-2003 年）和较新治疗时期（2004-2009 年）的结果。通过调整年龄、性别、体能评分、T 分期、N 分期、肿瘤单侧性和组织学分级的多变量 Cox 比例风险模型来比较两组的结果。结果 分析中纳入了 6 项随机试验中总共 6501 名接受 FOLFOX 或 FLOX 辅助治疗的 III 期结肠癌患者。新时代组入组的患者在复发时间方面经历了统计学上的显着改善[3 年复发率，76.1% 对比 73.0%；调整后的风险比 (HRadj) = 0.83 (95% CI, 0.74-0.92), P = 0.0008]，无病生存率 (DFS) [3 年率，74.7% 对比 72.3%； HRadj = 0.88 (0.79-0.98)，P = 0.024]，复发后生存率 (SAR) [中位时间，27.0 个月与 17.7 个月； HRadj = 0.65 (0.57-0.74)，P < 0.0001] 和总生存率 (OS) [5 年率，80.9% 对比 75.7%； HRadj = 0.78 (0.69-0.88)，P < 0.0001]。在 45 岁或以上诊断的患者、低风险患者（T1-3 和 N1）、左结肠、错配修复良好 (pMMR)、BRAF 和 KRAS 野生型肿瘤中，结果仍得到改善。 结论 与较早时期的患者相比，在 2004 年或之后接受 FOLFOX/FLOX 辅助治疗的临床试验中，观察到 III 期结肠癌患者的预后有所改善。 Prolonged SAR 要求重新验证 3 年 DFS 作为辅助临床试验中 OS 的替代终点，并重新评估 OS 的最佳随访，以根据 DFS 终点确认试验结果。临床试验编号 NCT00079274； NCT00096278； NCT00004931； NCT00275210； NCT00265811； NCT00112918。