Duration of Adjuvant Chemotherapy for Stage III Colon Cancer.
Duration of Adjuvant Chemotherapy for Stage III Colon Cancer.
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DOI：
10.1056/nejmoa1713709
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发表时间：
2018-03-29
期刊：
影响因子：
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通讯作者：
Iveson T
中科院分区：
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作者：
Grothey A;Sobrero AF;Shields AF;Yoshino T;Paul J;Taieb J;Souglakos J;Shi Q;Kerr R;Labianca R;Meyerhardt JA;Vernerey D;Yamanaka T;Boukovinas I;Meyers JP;Renfro LA;Niedzwiecki D;Watanabe T;Torri V;Saunders M;Sargent DJ;Andre T;Iveson T
自2004年以来，奥沙利铂联合氟尿嘧啶治疗6个月的方案已成为III期结肠癌患者的标准辅助治疗。然而，由于奥沙利铂与累积神经毒性相关，因此较短的治疗持续时间可以节省毒性作用和健康支出。我们对同时进行的6项随机、III期试验进行了前瞻性、预先计划的汇总分析，以评价FOLFOX（氟尿嘧啶、亚叶酸和奥沙利铂）或CAPOX（卡培他滨和奥沙利铂）辅助治疗3个月与6个月相比的非劣效性。主要终点是3年无病生存率。如果风险比的双侧95%置信区间的上限不超过1.12，则可以声明3个月治疗相对于6个月治疗的非劣效性。在12，834例患者中报告了3263起疾病复发或死亡事件后，在整个研究人群中未证实3个月治疗相对于6个月治疗的非劣效性（风险比，1.07; 95%置信区间[CI]，1.00至1.15）。观察到CAPOX（风险比，0.95; 95% CI，0.85 - 1.06）较短方案的非劣效性，但FOLFOX（风险比，1.16; 95% CI，1.06 - 1.26）未观察到。在联合治疗方案的探索性分析中，在T1、T2或T3和N1癌症患者中，3个月的治疗不劣于6个月，3年无病生存率分别为83.1%和83.3%（风险比，1.01; 95%CI，0.90 - 1.12）。在分类为T4、N2或两者兼有的癌症患者中，联合治疗6个月的无病生存率上级优于3个月（64.4% vs. 62.7%）（风险比，1.12; 95% CI，1.03 - 1.23; P = 0.01，优效性）。在接受FOLFOX或CAPOX辅助治疗的III期结肠癌患者中，在总体人群中未证实治疗3个月与6个月相比的非劣效性。然而，在接受CAPOX治疗的患者中，3个月的治疗与6个月一样有效，特别是在低风险亚组中。（由国家癌症研究所和其他机构资助。
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. 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. 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). 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.)