134 Background: We conducted a phase I/II trial of chemoradiotherapy (CRT) concurrent with S-1 and cisplatin to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and safety in patients with esophageal carcinoma. Methods: Eligibility criteria included histologically proven squamous cell or adeno carcinoma of the thoracic esophagus, clinical stage II/III excluded T4, PS 0-1, age 20 to 75, and no prior treatment. Chemotherapy consisted of administration of S-1 60-80 mg/m2/day on days 1-14, and cisplatin at 75 mg/m2on day 1, repeated twice every 4 weeks. Single daily radiation of 1.8 Gy in 28 fractions (total 50.4Gy) was given concurrently starting on day 1. For patients achieving an objective response after CRT, two additional cycles of chemotherapy were administered. The phase I part adopted the 3+3 cohort design. Planned sample size of 75 patients was calculated based on the weighting of threshold values of CR rate according to the registered proportion of T1-2 and T3. Results: Patient accrual was terminated early due to slow enrollment after 44 eligible patients were accrued from May 2007 to Sep 2011. Patient backgrounds were: 40 males, with median age 62 years, PS 0/1 (39/5), squamous cell carcinoma / adenocarcinoma (43/1), T1/T2/T3 (14/8/22) and N0/N1 (7/36). In the phase I part, two of six patients experienced DLTs at each level of S-1 (S-1 60 or 80 mg/m2/day). Considering treatment compliance, RD was determined as S-1 60 mg/m2/day. The CR rate, primary endpoint of phase II, was 59.5% (22/37; 90%CI, 44.6-73.1%; the weighted threshold, 57.2%; p=0.46) on central review. In the phase II part, 3-year progression-free survival was 47.3% and 3-year overall survival was 61.9%. Grade 3 or 4 toxicity in phase II part included leukopenia (57.9%) neutropenia (50%), hyponatremia (28.9%), anorexia (21.1%), anemia (18.4%), thrombocytopenia (18.4%), and febrile neutropenia (2.6%). No treatment-related deaths were observed. Conclusions: Although CRT with S-1 plus cisplatin showed acceptable toxicity and favorable 3-year survival, this study did not meet its primary endpoint. Clinical trial information: 000000710.