Sungkyunkwan University School of Medicine, Samsung Medical Centre, Seoul, South Korea.
Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
J Clin Oncol. 2022 Nov 20;40(33):3868-3877. doi: 10.1200/JCO.21.02962. Epub 2022 Jun 30.
The combination of oxaliplatin and fluoropyrimidine for 6 months is one of the standard options for adjuvant therapy for high-risk stage II and III colorectal cancers (CRCs). The optimal duration of oxaliplatin to diminish neurotoxicity without compromising efficacy needs to be clarified.
This open-label, randomized, phase III, noninferiority trial randomly assigned patients with high-risk stage II and III CRC to 3 and 6 months of oxaliplatin with 6 months of fluoropyrimidine groups (3- and 6-month arms, respectively). The primary end point was disease-free survival (DFS), and the noninferiority margin was a hazard ratio (HR) of 1.25.
In total, 1,788 patients were randomly assigned to the 6-month (n = 895) and 3-month (n = 893) arms, and 83.6% in the 6-month arm and 85.7% in the 3-month arm completed the treatment. The neuropathy rates with any grade were higher in the 6-month arm than in the 3-month arm (69.5% 58.3%; < .0001). The 3-year DFS rates were 83.7% and 84.7% in the 6-month and 3-month arms, respectively, with an HR of 0.953 (95% CI, 0.769 to 1.180; test for noninferiority, = .0065) within the noninferiority margin. Among patients with stage III CRC treated by capecitabine plus oxaliplatin, the 3-year DFS of the 3-month arm was noninferior as compared with that of the 6-month arm with an HR of 0.713 (95% CI, 0.530 to 0.959; = .0009). However, among patients with high-risk stage II and stage III CRC treated by infusional fluorouracil, leucovorin, and oxaliplatin, the noninferiority of the 3-month arm compared with the 6-month arm was not proven.
This study suggests that adding 3 months of oxaliplatin to 6 months of capecitabine could be considered an alternative adjuvant treatment for stage III CRC (ClinicalTrials.gov identifier: NCT01092481).
奥沙利铂联合氟嘧啶类药物治疗 6 个月是高危 II 期和 III 期结直肠癌（CRC）辅助治疗的标准选择之一。需要明确减少神经毒性而不影响疗效的奥沙利铂最佳持续时间。
这是一项开放标签、随机、III 期、非劣效性试验，将高危 II 期和 III 期 CRC 患者随机分配至接受 3 个月和 6 个月奥沙利铂联合 6 个月氟嘧啶组（3 个月和 6 个月组）。主要终点是无病生存期（DFS），非劣效性边界为风险比（HR）为 1.25。
共有 1788 例患者被随机分配至 6 个月（n=895）和 3 个月（n=893）臂，6 个月臂中 83.6%和 3 个月臂中 85.7%完成了治疗。6 个月臂的任何级别神经病变发生率高于 3 个月臂（69.5%比 58.3%；<0.0001）。6 个月臂和 3 个月臂的 3 年 DFS 率分别为 83.7%和 84.7%，HR 为 0.953（95%CI，0.769 至 1.180；非劣效性检验，=0.0065），在非劣效性边界内。在接受卡培他滨联合奥沙利铂治疗的 III 期 CRC 患者中，3 个月臂的 3 年 DFS 不劣于 6 个月臂，HR 为 0.713（95%CI，0.530 至 0.959；=0.0009）。然而，在接受氟尿嘧啶、亚叶酸和奥沙利铂输注治疗的高危 II 期和 III 期 CRC 患者中，3 个月臂与 6 个月臂的非劣效性未得到证实。
本研究表明，在卡培他滨治疗 6 个月的基础上加用 3 个月奥沙利铂可能是 III 期 CRC 的一种替代辅助治疗选择（ClinicalTrials.gov 标识符：NCT01092481）。
