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背景和目的卡培他滨联合奥沙利铂方案(CapeOX)是针对转移性结直肠癌患者的细胞毒化疗备选方案之一。而S-1联合奥沙利铂双药联合方案(SOX)具有很好的发展前景。本试验旨在比较CapeOX方案与SOX方案的有效性和安全性。方法本研究属于开放、多中心随机对照的Ⅲ期临床研究,来自韩国11个研究机构参与试验。符合入组标准的患者按照1∶1的比例随机接受CapeOX(第1~14天卡培他滨1 000 mg/m2,每日2次,并且第1天奥沙利铂130 mg/m2)和SOX方案(第1~14天S-1 40 mg/m2,每日2次,并且第1天奥沙利铂130 mg/m2)治疗。两者均为3周方案,包含奥沙利铂的联合化疗共9个疗程,除非在治疗中出现疾病进展、不能耐受的毒性反应和主观拒绝治疗。完成后允许进入卡培他滨或S-1单药治疗的维持期。试验以电脑生成的随机数列进行随机分组(按以下因素进行分层:原发病变部位、既往有无接受辅助或新辅助治疗以及是否存在可测量病灶)。试验的主要终点为SOX方案相对CapeOX方案显示出非劣效无进展生存(PFS)。统计分析来自意向治疗人群。本研究已在ClinicalTrials.gov注册,编号为NCT00677443。结果在2008年5月14日至2009年9月23日期间,共有168名患者接受SOX治疗方案,172名患者接受CapeOX方案。两者中位PFS分别为8.5个月(95%CI:7.6-9.3)和6.7个月(6.2~7.1,危险比RR=0.79,95%CI:0.60-1.04;非劣效P<0.0001,Log-rank检验P=0.09)。可信区间的上限低于预测值1.43,显示在PFS上,SOX方案劣于CapeOX方案。安全性方面,SOX组记录到3~4级粒细胞减少[49(29%)vs.24(15%)]、血小板减少[37(22%)vs.11(71%)]、腹泻[16(10%)vs.7(4%)]的发生率高于CapeOX组。但CapeOX组各级的手-足综合征发生率均高于SOX组[51(31%)vs.23(14%)]。结论 SOX方案有望成为转移性结直肠癌患者可供选择的一线双药联合化疗方案。有必要进一步试验探讨联合靶向药物及其在辅助化疗中的疗效。
Background and Objective Capecitabine and oxaliplatin regimen (CapeOX) is one of the cytotoxic chemotherapy options for patients with metastatic colorectal cancer. The S-1 combined with oxaliplatin dual-drug regimen (SOX) has good prospects for development. This test aims to compare the effectiveness and safety of the CapeOX and SOX programs. Methods This study was an open, multicenter, randomized phase III clinical trial involving 11 Korean research institutes. Patients who met the inclusion criteria were randomized to receive CapeOX (capecitabine 1 to 14 mg / m2 on day 1 to 14, twice daily and oxaliplatin 130 mg / m2 on day 1) in a 1: 1 ratio SOX regimen (S-1 40 mg / m2 on days 1-14, 2 times daily, and oxaliplatin 130 mg / m2 on day 1). Both are 3-week regimens and include oxaliplatin in combination with chemotherapy for a total of 9 cycles unless there is disease progression during the treatment, intolerable toxicity and subjective rejection therapy. When completed, capecitabine or S-1 monotherapy is permitted. Randomized, randomized, computer-generated randomized trials (stratified by primary lesion, past or present non-adjuvant or neoadjuvant and measurable lesions). The primary endpoint of the trial was SOX versus non-inferiority-free survival (PFS) over the CapeOX regimen. Statistical analysis from the intention to treat the crowd. This study is registered with ClinicalTrials.gov and is numbered NCT00677443. Results From May 14, 2008 to September 23, 2009, a total of 168 patients underwent SOX treatment and 172 patients underwent CapeOX. The median PFS was 8.5 months (95% CI 7.6-9.3) and 6.7 months (6.2-7.1, hazard ratio RR 0.79, 95% CI 0.60-1.04 respectively; noninferiority P <0.0001, Log -rank test P = 0.09). The upper limit of the confidence interval is lower than the predicted value of 1.43, shown on the PFS, and the SOX scheme is inferior to the CapeOX scheme. In terms of safety, grade 3 to 4 neutropenia (49 (29%) vs 24 (15%)), thrombocytopenia (37 22% vs 11 71%), diarrhea (10%) vs. 7 (4%)] were higher in the CapeOX group. However, the incidence of hand-foot syndrome at all levels in the CapeOX group was significantly higher than that in the SOX group [51 (31%) vs. 23 (14%)]. Conclusion The SOX regimen is expected to become an alternative first-line and dual-drug regimen in patients with metastatic colorectal cancer. Further testing is needed to explore the efficacy of the combination of targeted drugs and their use in adjuvant chemotherapy.