Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, P. R. China.
Department of Medical Oncology, Henan Cancer Hospital, Zhengzhou, 450008, Henan, P. R. China.
Cancer Commun (Lond). 2019 Apr 2;39(1):16. doi: 10.1186/s40880-019-0359-7.
The benefit of systemic treatments in esophageal squamous cell carcinoma (ESCC) which has progressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established. We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum- or taxane-based chemotherapy.
We conducted a prospective randomized, multicenter, open-label, phase 3 trial in 15 centers across China. Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC, and were randomly assigned (ratio, 1:1) to receive either irinotecan plus S-1 (intravenous infusion of irinotecan [160 mg/m] on day 1 and oral S-1 [80-120 mg] on days 1-10, repeated every 14 days) or oral S-1 monotherapy (80-120 mg/day on days 1-14, repeated every 21 days) using a central computerized minimization procedure. The primary endpoint was progression-free survival (PFS).
Between December 23, 2014 and July 25, 2016, we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen (n = 61) or S-1 monotherapy (n = 62). After a median follow-up of 29.2 months (95% confidence interval [CI] 17.5-40.9 months), the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group (3.8 months [95% CI 2.9-4.3 months] vs. 1.7 months [95% CI 1.4-2.7 months], hazard ratio = 0.58, 95% CI 0.38-0.86, P = 0.006). The objective response rates were 24.6% in the irinotecan plus S-1 group and 9.7% in the S-1 monotherapy group (P = 0.002). The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia (16.4% vs. 0%), neutropenia (14.8% vs. 1.6%), and nausea (4.9% vs. 0%). No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both groups.
The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurrent or metastatic ESCC. Clinical Trial Registration NCT02319187. Registered on December 9, 2014.
对于化疗后进展的食管鳞癌（ESCC）患者，全身治疗的获益仍不确定，也尚未基于随机试验确立最佳方案。我们旨在比较伊立替康联合 S-1 与 S-1 单药治疗对铂类或紫杉类化疗耐药的复发性或转移性 ESCC 患者的疗效。
我们在中国 15 家中心进行了一项前瞻性、随机、多中心、开放标签、3 期试验。符合条件的患者为组织学证实的复发性或转移性 ESCC 成年患者，随机（比例 1:1）接受伊立替康联合 S-1 治疗（第 1 天静脉滴注伊立替康[160mg/m]，第 1-10 天口服 S-1[80-120mg]，每 14 天重复一次）或 S-1 单药治疗（第 1-14 天每天口服 S-1[80-120mg]，每 21 天重复一次），使用中央计算机最小化程序进行分配。主要终点是无进展生存期（PFS）。
2014 年 12 月 23 日至 2016 年 7 月 25 日，我们筛选了 148 例患者，随机将 123 例患者分配至伊立替康联合 S-1 组（n=61）或 S-1 单药组（n=62）。中位随访 29.2 个月（95%置信区间 [CI] 17.5-40.9 个月）后，伊立替康联合 S-1 组的中位 PFS 明显长于 S-1 单药组（3.8 个月 [95% CI 2.9-4.3 个月] vs. 1.7 个月 [95% CI 1.4-2.7 个月]，风险比=0.58，95% CI 0.38-0.86，P=0.006）。伊立替康联合 S-1 组的客观缓解率为 24.6%，S-1 单药组为 9.7%（P=0.002）。伊立替康联合 S-1 组的 3-4 级白细胞减少症（16.4% vs. 0%）、中性粒细胞减少症（14.8% vs. 1.6%）和恶心（4.9% vs. 0%）发生率较高。两组均未观察到 3-4 级腹泻和与治疗相关的死亡。
与 S-1 单药治疗相比，伊立替康联合 S-1 作为复发性或转移性 ESCC 二线或三线治疗药物，耐受性相似，但 PFS 显著延长。临床试验注册 NCT02319187。于 2014 年 12 月 9 日注册。
Zotero 插件
