S-1 plus oxaliplatin versus capecitabine plus oxaliplatin for first-line treatment of patients with metastatic colorectal cancer: a randomised, non-inferiority phase 3 trial
S-1 plus oxaliplatin versus capecitabine plus oxaliplatin for first-line treatment of patients with metastatic colorectal cancer: a randomised, non-inferiority phase 3 trial
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DOI：
10.1016/s1470-2045(12)70363-7
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发表时间：
2012-11-01
期刊：
影响因子：
51.1
通讯作者：
Lee, Jae Won
中科院分区：
文献类型：
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作者：
Hong, Yong Sang;Park, Young Suk;Lee, Jae Won
背景卡培他滨加奥沙利铂（CapeOX）是治疗转移性结直肠癌患者的双重细胞毒化疗参考方案之一。我们旨在比较CapeOX与S-1 +奥沙利铂（SOX）的疗效和安全性，S-1 +奥沙利铂是转移性结直肠癌患者的一种有希望的替代治疗方法。在这项开放标签、多中心、随机化的3期试验中，我们随机分配了来自韩国11家机构的患者（1:1），接受CapeOX(卡培他滨1000 mg/m（2)，每天两次，第1-14天，奥沙利铂130 mg/m(2)，第1天）或SOX (S-1 40 mg/m（2)，每天两次，第1天，奥沙利铂130 mg/m(2)）。治疗每3周重复一次，并持续进行多达9个周期的含奥沙利铂化疗，除非出现疾病进展、不可接受的毒性或患者拒绝。奥沙利铂停药后允许S-1或卡培他滨维持化疗。随机化采用计算机生成的序列（按原发部位、既往辅助或新辅助治疗以及可测量病变的存在进行分层）。主要终点是在无进展生存期（PFS）方面显示SOX相对于CapeOX的非劣效性。初步分析是通过意向治疗。本研究已在ClinicalTrials.gov注册，注册号NCT00677443。在2008年5月14日至2009年9月23日期间，我们随机分配168名患者接受SOX治疗，172名患者接受CapeOX治疗。SOX组的中位PFS为8.5个月（95% CI 7.6-9.3）， CapeOX组的中位PFS为6.7个月（6.2-7.1）（风险比0.79 [95% CI 0.60-1.04]; p（非劣效性）< 0.0001,p(log-rank) = 0.09）。CI的上限低于预先设定的1.43，表明SOX对CapeOX的非劣效性。我们记录到SOX组中3-4级中性粒细胞减少症（49例[29%]vs 24例[15%]）、血小板减少症（37例[22%]vs 11例[7%]）和腹泻（16例[10%]vs 7例[4%]）的发生率高于CapeOX组。CapeOX组出现任何级别手足综合征的频率均高于SOX组（51例[31%]vs 23例[14%]）。SOX方案可能是转移性结直肠癌患者一线双重化疗方案的替代方案。需要进一步研究其与其他靶向药物联合使用或作为辅助化疗的潜力。资助韩国保健技术研究和发展项目，韩国卫生和福利部。
Background Capecitabine plus oxaliplatin (CapeOX) is one of the reference doublet cytotoxic chemotherapy treatments for patients with metastatic colorectal cancer. We aimed to compare the efficacy and safety of CapeOX with that of S-1 plus oxaliplatin (SOX), a promising alternative treatment for patients with metastatic colorectal cancer.Methods In this open-label, multicentre, randomised phase 3 trial, we randomly assigned patients (1: 1) from 11 institutions in South Korea to receive either CapeOX (capecitabine 1000 mg/m(2) twice daily on days 1-14 and oxaliplatin 130 mg/m(2) on day 1) or SOX (S-1 40 mg/m(2) twice daily on days 1-14 and oxaliplatin 130 mg/m(2) on day 1). Treatment was repeated every 3 weeks and continued for as many as nine cycles of oxaliplatin-containing chemotherapy, except in instances of disease progression, unacceptable toxicity, or a patient's refusal. Maintenance chemotherapy with S-1 or capecitabine was allowed after discontinuation of oxaliplatin. Randomisation was done with a computer-generated sequence (stratified by primary sites, previous adjuvant or neoadjuvant treatment, and the presence of measurable lesions). The primary endpoint was to show non-inferiority of SOX relative to CapeOX in terms of progression-free survival (PFS). The primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00677443.Findings Between May 14, 2008, and Sept 23, 2009, we randomly assigned 168 patients to receive SOX and 172 to receive CapeOX. Median PFS was 8.5 months (95% CI 7.6-9.3) in the SOX group and 6.7 months (6.2-7.1) in the CapeOX group (hazard ratio, 0.79 [95% CI 0.60-1.04]; p(non-inferiority) < 0.0001, p(log-rank) = 0.09). The upper limit of the CI was below the predefined margin of 1.43, showing the non-inferiority of SOX to CapeOX. We recorded a higher incidence of grade 3-4 neutropenia (49 [29%] vs 24 [15%]), thrombocytopenia (37 [22%] vs 11 [7%]), and diarrhoea (16 [10%] vs seven [4%]) in the SOX group than in the CapeOX group. The frequency of any grade of hand-foot syndrome was greater in the CapeOX group than it was in the SOX group (51 [31%] vs 23 [14%]).Interpretation The SOX regimen could be an alternative first-line doublet chemotherapy strategy for patients with metastatic colorectal cancer. Further investigation is needed to explore its potential when used together with other targeted agents or as adjuvant chemotherapy.Funding Korea Healthcare Technology Research and Development Project, Ministry of Health and Welfare, South Korea.