《新英格兰医学杂志》2018年3月29日378:1177-1188

DOI:10.1056/NEJMoa1713709

III期结肠癌辅助化疗的持续时间

背景

2004年以来，奥沙利铂联合一种氟嘧啶的6个月治疗方案已经成为III期结肠癌患者的标准辅助治疗方案，但由于奥沙利铂有神经累积毒性，更短的治疗持续时间可能会减轻毒副作用、减少医疗花费。

方法

我们实施了一项前瞻性、预先计划的对6个随机3期临床试验的汇总分析，这6个试验同步评价了3个月的FOLFOX方案（氟尿嘧啶、亚叶酸钙、奥沙利铂）、或CAPOX方案（卡培他滨和奥沙利铂）辅助治疗与6个月方案的非劣效性比较。主要终点为3年时的无病生存率。若风险比的双边95%置信区间上限未超过1.12，则3个月对比6个月治疗方案为非劣效。

结果

12834名患者中报告了3263个肿瘤复发或死亡事件后，进行的分析发现，在所有研究患者中未能证实3个月治疗对比6个月治疗方案的非劣效性（风险比，1.07；95%置信区间[CI]，1.00-1.15）。对于CAPOX方案，发现短程治疗方案的非劣效性（风险比，0.95；95%CI，0.85-1.06），但对于FOLFOX方案则发现非劣效性（风险比，1.16；95%CI，1.06-1.26）。在对合并治疗方案的探索性分析中，在肿瘤为T1、T2、T3和N1的患者中，3个月的治疗方案不劣于6个月方案，3年时的无病生存率分别为83.1%和83.3%（风险比，1.01；95%CI，0.90-1.12）。在分类为T4、N2或T4N2的癌症患者中，对于合并治疗方案，持续6个月治疗的无病生存率优于持续3个月治疗（64.4%对比62.7%）（风险比，1.12；95%CI，1.03-1.23；优效性检验P=0.01）。

结论

与6个月辅助治疗相比，在接受3个月的FOLFOX方案或CAPOX方案辅助治疗的III期结肠癌患者中，总体上未证实有非劣效性，但在用CAPOX治疗的患者中，尤其是在低危亚组中，3个月治疗与6个月治疗同样有效。

《壹篇》南南和北北

Duration of Adjuvant Chemotherapy for Stage III Colon Cancer

Background

Since 2004, a regimen of 6 months of treatment with oxaliplatin plus a fluoropyrimidine has been standard adjuvant therapy in patients with stage III colon cancer. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy could spare toxic effects and health expenditures.

Methods

We performed a prospective, preplanned, pooled analysis of six randomized, phase 3 trials that were conducted concurrently to evaluate the noninferiority of adjuvant therapy with either FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) administered for 3 months, as compared with 6 months. The primary end point was the rate of disease-free survival at 3 years. Noninferiority of 3 months versus 6 months of therapy could be claimed if the upper limit of the two-sided 95% confidence interval of the hazard ratio did not exceed 1.12.

Results

After 3263 events of disease recurrence or death had been reported in 12,834 patients, the noninferiority of 3 months of treatment versus 6 months was not confirmed in the overall study population (hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15). Noninferiority of the shorter regimen was seen for CAPOX (hazard ratio, 0.95; 95% CI, 0.85 to 1.06) but not for FOLFOX (hazard ratio, 1.16; 95% CI, 1.06 to 1.26). In an exploratory analysis of the combined regimens, among the patients with T1, T2, or T3 and N1 cancers, 3 months of therapy was noninferior to 6 months, with a 3-year rate of disease-free survival of 83.1% and 83.3%, respectively (hazard ratio, 1.01; 95% CI, 0.90 to 1.12). Among patients with cancers that were classified as T4, N2, or both, the disease-free survival rate for a 6-month duration of therapy was superior to that for a 3-month duration (64.4% vs. 62.7%) for the combined treatments (hazard ratio, 1.12; 95% CI, 1.03 to 1.23; P=0.01 for superiority).

Conclusions

Among patients with stage III colon cancer receiving adjuvant therapy with FOLFOX or CAPOX, noninferiority of 3 months of therapy, as compared with 6 months, was not confirmed in the overall population. However, in patients treated with CAPOX, 3 months of therapy was as effective as 6 months, particularly in the lower-risk subgroup. (Funded by the National Cancer Institute and others.)

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