替吉奥胶囊联合持续静脉滴注伊立替康加贝伐珠单抗对比 FOLFIRI 联合贝伐珠单抗一线治疗转移性结直肠癌的开放性随机 II 期临床试验
Oral S-1 with 24-h Infusion of Irinotecan plus Bevacizumab versus FOLFIRI plus Bevacizumab as First-Line Chemotherapy for Metastatic Colorectal Cancer: An Open-Label Randomized Phase II Trial.
机构信息
Department of Surgery, Tokai University, School of Medicine, Isehara, Japan,
Department of Surgery, Tokai University, School of Medicine, Isehara, Japan.
出版信息
Oncology. 2020;98(9):637-642. doi: 10.1159/000507293. Epub 2020 May 29.
BACKGROUND
FOLFIRI plus bevacizumab have been widely used as first-line treatment for metastatic colorectal cancer (mCRC). Pharmacokinetics and pharmacodynamics suggested a low dose of irinotecan given as a long-term infusion is expected to enhance antitumor activity. We conducted a randomized phase II study to compare oral S-1 with a 24-h infusion of irinotecan plus bevacizumab versus FOLFIRI plus bevacizumab.
METHODS
The subjects comprised 120 chemotherapy-naïve patients with mCRC. The study group received a 24-h infusion of irinotecan at a dose of 125 mg/m2 on days 1 and 15, combined with oral S-1 80 mg/m2 on days 1-14 (24h-SIRI/B). The FOLFIRI/B group received irinotecan at a dose of 150 mg/m2, 5-fluorouracil given at a dose of 400 mg/m2 as a bolus injection and at a dose of 2,400 mg/m2 as a 46-h infusion, and 200 mg/m2 leucovorin on days 1 and 15. Bevacizumab was given at a dose of 5.0 mg/kg on days 1 and 15 in both groups. Treatment was repeated every 4 weeks. The primary endpoint was 1-year progression-free survival (PFS). Secondary endpoints were PFS, response rates (RR), overall survival (OS), and adverse events (AEs).
RESULTS
From December 2013 through January 2018, 120 patients were randomly assigned, 61 patients to the 24h-SIRI/B and 59 patients to the FOLFIRI/B. The median follow-up period was 22.8 months. The 1-year PFS rate was 43.14% in the 24h-SIRI/B arm and 19.15% in the FOLFIRI/B arm (HR = 0.312 [95%CI 0.13-0.78], p = 0.01). The median PFS was 10.2 months (95%CI 8.8-14.3) and 10.0 months (95%CI 7.4-11.0), and the median OS was 29.7 months (95%CI 22.9-43.9) and 28.8 months (95%CI 18.4-ND), respectively (p = 0.3758, p = 0.8234). The overall RR was 86.3 and 61.7%, respectively (p = 0.0053). AEs were similar.
CONCLUSIONS
Our results show that the 24h-SIRI/B regimen is an effective and reasonably well-tolerated regimen for the first-line treatment of mCRC.
背景
FOLFIRI 联合贝伐珠单抗已广泛用于转移性结直肠癌（mCRC）的一线治疗。药代动力学和药效学研究表明，低剂量伊立替康持续输注有望增强抗肿瘤活性。我们进行了一项随机 II 期研究，比较了 S-1 口服与伊立替康 24 小时输注联合贝伐珠单抗与 FOLFIRI 联合贝伐珠单抗的疗效。
方法
本研究纳入了 120 例初治 mCRC 患者。研究组患者接受伊立替康 125mg/m2 持续输注 24 小时，联合 S-1 80mg/m2 口服，每日 1-14 天（24h-SIRI/B 方案）。FOLFIRI/B 组患者接受伊立替康 150mg/m2，5-氟尿嘧啶 400mg/m2 推注，2400mg/m2 持续输注，亚叶酸钙 200mg/m2，第 1 和第 15 天给药。两组患者均在第 1 和第 15 天接受贝伐珠单抗 5.0mg/kg 治疗。每 4 周重复一次治疗。主要终点为 1 年无进展生存期（PFS）。次要终点为 PFS、缓解率（RR）、总生存期（OS）和不良事件（AEs）。
结果
2013 年 12 月至 2018 年 1 月，共纳入 120 例患者，随机分为 24h-SIRI/B 组（n=61）和 FOLFIRI/B 组（n=59）。中位随访时间为 22.8 个月。24h-SIRI/B 组和 FOLFIRI/B 组的 1 年 PFS 率分别为 43.14%和 19.15%（HR=0.312[95%CI 0.13-0.78]，p=0.01）。中位 PFS 分别为 10.2 个月（95%CI 8.8-14.3）和 10.0 个月（95%CI 7.4-11.0），中位 OS 分别为 29.7 个月（95%CI 22.9-43.9）和 28.8 个月（95%CI 18.4-ND）（p=0.3758，p=0.8234）。总的 RR 分别为 86.3%和 61.7%（p=0.0053）。两组 AEs 相似。
结论
我们的研究结果表明，24h-SIRI/B 方案是一种有效且耐受性良好的 mCRC 一线治疗方案。
Zotero 插件