Abstract: Objective: To compare the effects of and adverse reactions to NDP+5-FU with syn-chronous radiotherapy and those of DDP +5 -FU with concurrent radiotherapy in the treatment of esophageal cancer. Methods: From November 2003 to December 2004, 80 cases with advanced esophageal carcinoma were randomly divided into two groups: concurrent chemoradiotherapy with NDP and 5-FU (the trial group, n=42) and synchronous chemoradiotherapy with DDP and 5-FU (the control group, n=38). The patients in these two groups were treated with conventional fractionated radiotherapy at 2.0 Gy/f, with a total dose of 66 Gy/33Fx/45d. Chemotherapy regime was delivered on the first day of radiotherapy. The chemotherapy in the trial group consisted of 2 cycles of NDP at 60mg/ (m2 · d) on day 1 plus 5-FU at 500 mg/(m2 · d) on day 1 to 5 every 4 weeks, and the control group consisted of 2 cycles of DDP at 30mg/(m2 · d) on day 1 to 3 plus 5-FU at 500 mg/ (m2 · d) on day 1 to 5 every 4 weeks.Results: The overall response (CR+PR) rate was 78.6% in the trial group and 60.5% in the control group (P<0.05). The 1-year local control rate and survival rate were 83.3% and 59.5% in the trial group, and 68.4% and 39.5% in the control group, respectively(P<0.05). The incidence of major adverse effects in the trial group such as nausea and vomiting were lower compared to that in the control group (P <0.05). Conclusions: NDP +5 -FU combined with radiotherapy can effectively treat advanced esophageal cancer. It shows reduced side effects compared to DDP+5-FU. However, further study is needed for longer-term curative effect of the regimen, which should involve more patients and a prolonged follow-up. Larger sample studies with randomization must be included.