Background and purpose:Concurrent radiochemotherapy is the standard modality for locally advanced esophageal squamous cell carcinoma (ESCC) patients. This clinical trial aimed to assess the effectiveness and toxicity of continuous infusion of 5-lfuorouracil (5-FU) and weekly paclitaxel combined with radiotherapy in ESCC patients. Methods:Patients with locally advanced (T2-4N0-1M0-1a) esophageal squamous cell carcinoma were enrolled in a prospective, single-institutional, single-arm study of deifnitive chemoradiotherapy. Patients received 61.2 Gy with IMRT in 34 fractions. Patients had a Karnofsky performance status of 70 or greater, and normal liver, renal, and bone marrow functions. Patients were recommended to receive concurrent 5-FU (300 mg/m2 civ 96 h) for 5 days a week for 5 weeks, plus paclitaxel (50 mg/m2) given during 3 hours every week for 5 weeks. Patients were recommended to receive 2 courses of consolidation chemotherapy after concurrent radio (chemo) therapy (5-FU 1 800 mg/m2 civ 72 h, plus paclitaxel 175 mg/m2 every 28 days). The primary endpoints of the study were 5 year overall survival and acute toxicity. Results:Fifty patients were enrolled in this study, including 38 male patients and 12 female patients;median age:58 years (ranged 26 to 75 years). 72%patients completed all the chemotherapy and 98%patients received the full dose of radiotherapy. 1-, 2-, 3-, and 5-year survival were 75%, 56%, 42%and 28%respectively. Among haematological toxicities, grade 3 leukopenia (16%) was recorded, and no patients experienced any≥grade 2 thrombocytopenia or anaemia. Among non-haematological toxicities, the rates of grade 2 peripheral neurotoxicity, arthralgias and myalgias, nausea, vomiting, and fatigue were 8%, 4%, 4%, 2%and 6%respectively. The rates of≥grade 2 acute radiation-induced esophageal toxicity, radiation pneumonitis and skin toxicity were 32%, 44% and 14% respectively. No treatment-related deaths occurred and no patients experienced any ≥ grade 4 toxicities. Conclusion: Continuous infusion of 5-FU plus paclitaxel given concurrently with radiotherapy may be an effective and tolerable treatment option for ESCC patients.