129 Background: Neoadjuvant chemotherapy with cisplatin (CDDP) plus 5-fluorouracil (5-FU) is considered the standard treatment for stage II/III esophageal squamous cell carcinoma (ESCC) in Japan. However, patient survival remains unsatisfactory and neoadjuvant chemoradiotherapy (NeoCRT) may improve the outcome of stage II/III ESCC patients. We conducted a feasibility study of NeoCRT with CDDP plus 5-FU and elective nodal irradiation in patients with stage II/III ESCC. Methods: Eligibility criteria included clinical stage II/III (UICC 6th, non-T4) ESCC, a Performance status (PS) of 0-1, and age of 20–75 years. Chemotherapy consisted of 2 courses of 5-FU infusion (1000 mg/m2, days 1–4) and a 2-h CDDP infusion (75 mg/m2, day 1), with a 4-week interval. Radiotherapy was concurrently administered to the primary tumor, metastatic lymph nodes, and regional lymph nodes (total dose of 41.4 Gy in 23 fractions. After completion of NeoCRT, transthoracic esophagectomy with extensive lymphadenectomy (>D2) was performed. The primary endpoint was the completion rate of NeoCRT with R0 resection. Results: Thirty-three patients were enrolled in this study between July 2010 and June 2011 and 2 were determined to be ineligible. Characteristics of the 31 eligible patients included, a median age of 63 years (range, 40–73 years), male/female: 28/3, PS 0/1: 19/12, and cStage IIA/IIB/III: 2/10/19. Median observation time was 30.0month. In total, 29 patients (93.5%) underwent NeoCRT with R0 resection. Among the patients who underwent surgery, there was 1 treatment-related death, and the incidence of operative morbidity was similar to that in previous studies. According to RECIST, the overall response rate was 78% (14/18) after CRT. Pathological complete response was achieved in 13 patients (42%) who underwent esophagectomy. The 2 years recurrence free survival rate 69.8%, and 2 years survival rate was77.4%, respectively. Conclusions: NeoCRT was well tolerated and found to be highly promising. A randomized controlled trial (JCOG1109) comparing with neoadjuvant chemotherapy was started. Clinical trial information: UMIN000004223.