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Randomized Controlled Trial of Irinotecan Plus S-1 for Pretreated Patients with Advanced Esophageal Squamous Cell Carcinoma
66 Pages Posted: 24 Sep 2018
More...Abstract
Background: The benefit of systemic treatments in advanced esophageal squamous cell carcinoma (ESCC) patients progressing after chemotherapy is still uncertain and optimal regimens based on randomised trials have not been established. We aimed to compare irinotecan plus S-1 with S-1 monotherapy in previously treated advanced ESCC.
Methods: We conducted a multicentre, open-label, randomised trial in 16 centres in China. Eligible patients were adults with advanced, histologically confirmed ESCC, and were randomly assigned (1:1) to receive either irinotecan plus S-1 (IS) or S-1 alone using a central computerized minimization procedure. The IS group received intravenous irinotecan (160 mg/m2) on day 1 and oral S-1 (80-120 mg) on days 1-10, repeated every 14 days. The S-1 group received the same dose of S-1 on days 1-14, repeated every 21 days. The primary endpoint was progression-free survival (PFS) analysed by intention-to-treat. This trial is registered with ClinicalTrials.gov (NCT02319187).
Findings: Between December 23, 2014 and July 25, 2016, we screened 148 patients and randomly assigned 123 patients to receive either IS regimen (n=61) or S-1 (n=62). After a median follow-up of 29.2 months (95%CI 17.5-40.9), PFS was significantly better in the IS group than it was in the S-1 group (hazard ratio 0.58, 95% CI 0.38-0.86, p=0.003; median PFS 3.8 months [95% CI 3.1-4.6] in the IS group vs. 1.7 months [95% CI 1.0-2.4] in the S-1 group). The overall response rate was 24.6% in the IS group and 9.7% in the S group (p=0.028). The addition of irinotecan was associated with increased rates of grade 3-4 leukopenia (16.4% vs. 0%) and neutropenia (14.8% vs. 1.6%). No treatment-related deaths were observed in both groups.
Interpretation: The combination of irinotecan with S-1 significantly improved PFS compared with S-1 alone in pretreated advanced ESCC patients. Adverse events of both regimens were generally consistent with the known safety profiles in other malignancies.
Funding: National Key Basic Research Program of China (973 Program)
Declaration of Interest: No conflict of interest.
Ethical Approval: The project protocol was reviewed and approved by the Institutional Review Board (IRB) and ethical committees at icddr,b, and Dhaka Medical College and Hospital Dhaka, Bangladesh. Written informed consent was obtained from all participants or their legal representatives.
Keywords: Esophageal Squamous Cell Carcinoma; Irinotecan; S-1
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