结肠癌辅助奥沙利铂-氟嘧啶联合治疗 3 个月与 6 个月（SCOT）：一项国际性、随机、III 期、非劣效性试验。

BACKGROUND: 6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment. METHODS: The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1:1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1·13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing. FINDINGS: 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76·7% (95% CI 75·1-78·2) for the 3 month group and 77·1% (75·6-78·6) for the 6 month group, giving a hazard ratio of 1·006 (0·909-1·114, test for non-inferiority p=0·012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group). INTERPRETATION: In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care. FUNDING: Medical Research Council, Swedish Cancer Society, NETSCC, and Cancer Research UK.

背景：含奥沙利铂的化疗通常作为 3 期结直肠癌的辅助治疗。我们研究了 3 个月的含奥沙利铂化疗是否不劣于通常的 6 个月治疗。

方法：SCOT 研究是一项国际、随机、3 期、非劣效性试验，在 244 个中心进行。年龄在 18 岁或以上、患有高危 II 期和 III 期结直肠癌的患者进行中心随机分组，最小化中心、方案选择、性别、疾病部位、N 期、T 期和卡培他滨起始剂量。患者被分配（1:1）接受 3 个月或 6 个月的辅助含奥沙利铂化疗。化疗方案可包括 CAPOX（卡培他滨和奥沙利铂）或 FOLFOX（奥沙利铂联合氟尿嘧啶持续输注）。方案在随机分组前根据患者和治疗医生的选择进行选择。主要研究终点是无病生存期，非劣效性边界是危险比 1.13。主要分析在意向治疗人群中进行，安全性在开始研究治疗的患者中进行评估。这项试验在 ISRCTN 注册，编号 ISRCTN59757862，随访仍在继续。

发现：2008 年 3 月 27 日至 2013 年 11 月 29 日期间，6088 名患者进行了随机分组。1981 名患者接受 FOLFOX 治疗，4107 名患者接受 CAPOX 治疗。3044 名患者被分配到 3 个月组，3044 名患者被分配到 6 个月组。3 个月组中有 9 名患者和 6 个月组中有 14 名患者不同意使用其数据，因此 3 个月组中有 3035 名患者和 6 个月组中有 3030 名患者进行意向治疗分析。在分析截止日期，有 1482 例无病生存事件，3 个月组中有 740 例，6 个月组中有 742 例。3 年无病生存率为 3 个月组 76.7%（95%CI 75.1-78.2），6 个月组为 77.1%（75.6-78.6），危险比为 1.006（0.909-1.114，非劣效性检验 p=0.012），显著低于非劣效性边界。6 个月组（409 例患者中有 237 例[58%]有安全性数据）的 2 级或更高级别的周围神经病变比 3 个月组（420 例中有 103 例[25%]）更常见，且持续时间较长，与生活质量较差有关。报告了 1098 例严重不良事件（3 个月组报告 492 例，6 个月组报告 606 例）和 32 例与治疗相关的死亡（每组 16 例）。

解释：在整个研究人群中，3 个月的含奥沙利铂辅助化疗与高危 II 期和 III 期结直肠癌患者的 6 个月相同治疗不劣效，且与降低毒性和提高生活质量相关。尽管研究的效力不足，但这些数据表明较短的治疗时间可带来相似的生存结果，同时具有更好的生活质量，因此可能代表一种新的治疗标准。

资助：英国医学研究理事会、瑞典癌症协会、NETSCC 和英国癌症研究中心。