A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC).
A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC).
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DOI：
10.1093/annonc/mdw162
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发表时间：
2016-07
期刊：
影响因子：
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通讯作者：
Maehara Y
中科院分区：
文献类型：
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作者：
Oki E;Murata A;Yoshida K;Maeda K;Ikejiri K;Munemoto Y;Sasaki K;Matsuda C;Kotake M;Suenaga T;Matsuda H;Emi Y;Kakeji Y;Baba H;Hamada C;Saji S;Maehara Y
这项III期研究是第一项证明新的口服氟尿嘧啶S-1在无复发生存期方面优于替加氟-尿嘧啶作为未经术前治疗的II/III期直肠癌患者辅助化疗的研究。S-1可以被认为是一个重要的选择，特别是对于那些没有接受术前治疗的患者。预防远处复发和实现局部控制是直肠癌治疗的重要挑战，并且已经研究了辅助化疗的使用。然而，没有III期研究比较直肠癌的辅助化疗方案已经证明了特定方案的优越性。因此，我们进行了一项III期研究，以评价S-1在直肠癌辅助治疗中相对于替加氟-尿嘧啶（UFT）的优效性，替加氟-尿嘧啶是日本II/III期直肠癌根治性切除术的标准辅助化疗方案。ACTS-RC试验是一项在日本222家研究中心进行的开放标签、随机化、III期优效性试验。年龄在20-80岁的II/III期直肠癌患者接受根治性手术，术前未接受治疗，随机分配接受UFT（500-600 mg/天，第1-5天，随后停药2天）或S-1（80-120 mg/天，第1-28天，随后停药14天）治疗1年。主要终点是无复发生存期（RFS），次要终点是总生存期和不良事件。2006年4月至2009年3月，共入组961例患者。在分配接受UFT的480例患者和分配接受S-1的479例患者中进行了主要分析。UFT的5年RFS为61.7% [95%置信区间（CI）57.1%-65.9%]，S-1为66.4%（95% CI 61.9%-70.5%）[P = 0.0165，风险比（HR）：0.77，95% CI 0.63-0.96]。UFT的5年生存率为80.2%（95% CI 76.3%至83.5%），S-1为82.0%（95% CI 78.3%至85.2%）。UFT组的主要3级或以上不良事件为丙氨酸氨基转移酶升高和腹泻（各2.3%），S-1组为厌食、腹泻（各2.6%）和疲乏（2.1%）。1年S-1治疗在RFS方面上级UFT，因此已成为II/III期直肠癌根治性切除术后的标准辅助化疗方案。
This phase III study is the first study to demonstrate the superiority of new oral fluoropyrimidine S-1 over tegafur–uracil as adjuvant chemotherapy for stage II/III rectal cancer patients with no preoperative treatment in terms of relapse-free survival. S-1 can be considered an important option, especially for patients who have not received preoperative treatment. Preventing distant recurrence and achieving local control are important challenges in rectal cancer treatment, and use of adjuvant chemotherapy has been studied. However, no phase III study comparing adjuvant chemotherapy regimens for rectal cancer has demonstrated superiority of a specific regimen. We therefore conducted a phase III study to evaluate the superiority of S-1 to tegafur–uracil (UFT), a standard adjuvant chemotherapy regimen for curatively resected stage II/III rectal cancer in Japan, in the adjuvant setting for rectal cancer. The ACTS-RC trial was an open-label, randomized, phase III superiority trial conducted at 222 sites in Japan. Patients aged 20–80 with stage II/III rectal cancer undergoing curative surgery without preoperative therapy were randomly assigned to receive UFT (500–600 mg/day on days 1–5, followed by 2 days rest) or S-1 (80–120 mg/day on days 1–28, followed by 14 days rest) for 1 year. The primary end point was relapse-free survival (RFS), and the secondary end points were overall survival and adverse events. In total, 961 patients were enrolled from April 2006 to March 2009. The primary analysis was conducted in 480 assigned to receive UFT and 479 assigned to receive S-1. Five-year RFS was 61.7% [95% confidence interval (CI) 57.1% to 65.9%] for UFT and 66.4% (95% CI 61.9% to 70.5%) for S-1 [P = 0.0165, hazard ratio (HR): 0.77, 95% CI 0.63–0.96]. Five-year survival was 80.2% (95% CI 76.3% to 83.5%) for UFT and 82.0% (95% CI 78.3% to 85.2%) for S-1. The main grade 3 or higher adverse events were increased alanine aminotransferase and diarrhea (each 2.3%) in the UFT arm and anorexia, diarrhea (each 2.6%), and fatigue (2.1%) in the S-1 arm. One-year S-1 treatment is superior to UFT with respect to RFS and has therefore become a standard adjuvant chemotherapy regimen for stage II/III rectal cancer following curative resection.