A Phase II Trial of Definitive Chemoradiotherapy with S-1 and Cisplatin for Locally advanced Oesophageal Cancer

ABSTRACT Objectives S-1 is an orally active fluoropyrimidine with low gastrointestinal toxicity, capable of enhancing the efficacy of radiotherapy. We report a phase II study of chemoradiotherapy (CRT) combined with S-1 plus cisplatin for locally advanced esophageal cancer (LAEC). Methods CRT comprised two courses: 30-Gy radiotherapy over 3 weeks, plus daily oral S-1 (80 mg/m2/day) for 2 weeks, and a 24-h cisplatin infusion (70 mg/m2) on Day 8. A second identical course was administered after a 2-week break. If patients could not swallow the oral S-1 capsule, it was administered in powder form. In patients who showed an objective response to CRT, at least 2 courses of chemotherapy with S-1 and cisplatin were administered. Results Eighty-three patients participated, 12 with Stage II and 71 with Stage III LAEC. Seventy-seven patients (92.7%) completed CRT. The most frequent adverse events were Grades 3 and 4 neutropenia (38.6%); thrombocytopenia (13.3%), and anemia (9.6%). One patient died on Day 20 from febrile bone marrow aplasia. Non-hematological adverse events were mild. The most common were Grade 2 nausea (32.5%); esophageal pain and oral mucositis (16.9% each); and renal dysfunction (10.8%). Adverse events from the first course of CRT resolved during the 2 weeks interval. Complete response rates in patients with Stage II and Stage III LAEC were 91.7% and 67.6%, respectively. No relapse occurred in patients with Stage II disease, and relapses occurred in 21 (43.8%) of 48 patients with Stage III disease who achieved CR. Median PFS for patients with Stage II and III patients was 6.6 and 1.6 years, respectively. Median survival time was 7 years for Stage II and 2.6 years for Stage III LAEC. Conclusions CRT combined with S-1 plus cisplatin showed promising safety and efficacy, as well as potential to become a standard treatment for LAEC. Disclosure All authors have declared no conflicts of interest.