S-1 is a newly developed oral fluoropyrimidine derivative with demonstrated activity against several tumor types. The aim of this study was to evaluate the feasibility and efficacy of S-1 administered as a single-agent and in combination with cisplatin, for the treatment of patients with pancreatic cancer. A total of 33 patients with locally advanced or recurrent pancreatic cancer were entered into this study. Seventeen patients were treated with S-1 alone (group A), and 16 patients were treated with S-1 plus weekly cisplatin (group B). Objective tumor responses among the 15 evaluable patients in group A were 1 CR, 2 PR, 9 SD and 3 PD, and among the 14 evaluable patients in group B were 8 PR, 5 SD, and 1 PD. The overall response rates were 20.0% and 57.1% in groups A and B respectively. Seven of the 17 patients in group A with elevated CA19-9 serum concentration and 12 of the 13 patients in group B with elevated CA19-9 level, reduced their CA19-9 by more than 50%. The median follow-up periods/median durations of response were 152/102 days in group A and 105/66 days in group B. Median survivals have not been reached in either group. In group A, no patient developed severe toxicities over grade 3, but in group B, 3 patients developed hematotoxicity over grade 3, and 2 patients experienced grade 3 anorexia. S-1, especially in combination with CDDP, shows promising activity with acceptable toxicities against pancreatic cancer. Further evaluation of this combination in patients with this disease is warranted.