A prospective phase II trial of S-1 and cisplatin-based chemoradiotherapy for locoregionally advanced esophageal cancer

Purpose: S-1 is a novel oral fluoropyrimidine anticancer agent designed to enhance clinical efficacy, reduce gastrointestinal toxicity, and enhance radiotherapy effectiveness. A phase II trial was conducted to evaluate the efficacy and safety of preoperative chemoradiation with S-1 and cisplatin in locoregionally advanced esophageal cancer. Methods: Eligible patients had stage IIA-IVA esophageal cancer. Patients received two cycles of S-1 (days 1-14 and days 22-35) and cisplatin (days 1 and 22) with concurrent radiotherapy (50.4 Gy total; 1.8 Gy/fraction). Esophagectomy was performed between weeks 12 and 18 as determined by the specialist multidisciplinary team. Results: Sixty patients were enrolled in this study between March 2008 and August 2011, and 59 were eligible. The clinical stage was ≥ T3 in 28 patients (47 %) and N1 in 43 patients (72 %), with squamous cell carcinoma histology in 58 patients (97 %). Fifty-four patients (90 %) completed the planned chemoradiation. After chemoradiation, the clinical tumor response rate was 64.4 %. The primary toxicities included neutropenia (24 %) and esophagitis (8.5 %). Three treatment-related deaths were noted. Twenty-five patients (42 %) underwent esophagectomy following chemoradiation, and 15 achieved complete pathologic regression. The estimated overall survival and progression-free survival rates after 2 years were 65 and 48 %, respectively. Conclusions: Concurrent chemoradiation with S-1 and cisplatin exhibited encouraging results with complete pathologic regression. The survival data were promising compared with the historical data of 5FU/cisplatin and should be confirmed in a randomized phase III trial. Toxicities were significant but clinically manageable.