奥沙利铂为基础的辅助化疗时间（3 个月与 6 个月）用于高危 II 期结直肠癌：随机 III 期 ACHIEVE-2 试验。
Oxaliplatin-based adjuvant chemotherapy duration (3 versus 6 months) for high-risk stage II colon cancer: the randomized phase III ACHIEVE-2 trial.
机构信息
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
Department of Biostatistics, Yokohama City University School of Medicine, Kanagawa, Japan.
出版信息
Ann Oncol. 2021 Jan;32(1):77-84. doi: 10.1016/j.annonc.2020.10.480. Epub 2020 Oct 26.
BACKGROUND
Oxaliplatin-based adjuvant chemotherapy may be associated with debilitating peripheral sensory neuropathy (PSN) in patients with high-risk stage II colon cancer. This open-label, multicenter, randomized phase III trial was conducted as a prospective pooled analysis to investigate the non-inferiority of 3 versus 6 months of adjuvant oxaliplatin-based chemotherapy.
PATIENTS AND METHODS
From 12 February 2014 to 31 January 2017, 525 Asian patients with high-risk stage II colon cancer were randomly assigned to 3- and 6-month treatment arms. The treatment consisted of either modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine combined with oxaliplatin (CAPOX). The primary end point was disease-free survival (DFS). The secondary end points were treatment compliance and safety.
RESULTS
Of the 525 randomized patients, 11 were not treated. Among the 514 participating patients (255 in the 3-month arm; 259 in the 6-month arm), 432 (84%) received CAPOX, and 184 (36%) presented with T4 as a high-risk factor for recurrence. The 3-year DFS rate was 88.2% in the 3-month arm and 87.9% in the 6-month arm [hazard ratio (HR), 1.12; 95% confidence interval (CI), 0.67-1.87]. With CAPOX, the 3-year DFS rate was 88.2% in the 3-month arm and 88.4% in the 6-month arm (HR, 1.13; 95% CI, 0.65-1.96). The discontinuation rate in the 3- and 6-month arms was 10% and 31% for mFOLFOX6 (P = 0.0193), and 15% and 35% for CAPOX (P < 0.0001), respectively. The incidence of grade ≥2 PSN was significantly lower in the 3-month arm than in the 6-month arm (16% and 43%, respectively, P < 0.0001).
CONCLUSIONS
Three months of combination therapy presented significantly less grade ≥2 PSN than the respective 6-month regimen. The shortened therapy duration did not affect the 3-year DFS rate, suggesting that a 3-month course of CAPOX can be an effective treatment option.
CLINICAL TRIAL INFORMATION
UMIN Clinical Trials Registry, UMIN000013036 and Japan Registry of Clinical Trials, jRCTs031180128.
背景
奥沙利铂为基础的辅助化疗可能与高风险 II 期结肠癌患者的衰弱性周围感觉神经病变（PSN）有关。这项开放标签、多中心、随机 III 期试验是作为一项前瞻性汇总分析进行的，旨在研究 3 个月与 6 个月奥沙利铂为基础的辅助化疗的非劣效性。
患者和方法
2014 年 2 月 12 日至 2017 年 1 月 31 日，525 名高风险 II 期结肠癌亚洲患者被随机分配到 3 个月和 6 个月治疗组。治疗包括改良氟尿嘧啶、亚叶酸钙和奥沙利铂（mFOLFOX6）或卡培他滨联合奥沙利铂（CAPOX）。主要终点是无病生存期（DFS）。次要终点是治疗依从性和安全性。
结果
在 525 名随机患者中，有 11 名未接受治疗。在 514 名参与患者（3 个月组 255 名；6 个月组 259 名）中，432 名（84%）接受 CAPOX 治疗，184 名（36%）有 T4 作为复发的高危因素。3 年 DFS 率在 3 个月组为 88.2%，在 6 个月组为 87.9%[风险比（HR），1.12；95%置信区间（CI），0.67-1.87]。在使用 CAPOX 的情况下，3 个月组的 3 年 DFS 率为 88.2%，6 个月组为 88.4%（HR，1.13；95%CI，0.65-1.96）。在 3 个月和 6 个月组中，mFOLFOX6 的停药率分别为 10%和 31%（P=0.0193），CAPOX 的停药率分别为 15%和 35%（P<0.0001）。3 个月组的≥2 级 PSN 发生率明显低于 6 个月组（分别为 16%和 43%，P<0.0001）。
结论
与相应的 6 个月方案相比，3 个月的联合治疗方案显著降低了≥2 级 PSN 的发生率。缩短治疗时间并不影响 3 年 DFS 率，这表明 CAPOX 的 3 个月疗程可以作为一种有效的治疗选择。
临床试验信息
UMIN 临床试验注册，UMIN000013036 和日本临床试验注册，jRCTs031180128。
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