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S-1 is a new oral fluoropyrimidine anticancer agent shown to be effective for pancreatic cancer.In a previous phase I trial, we evaluated the safety of S-1 combined with radiotherapy to determine the maximum tolerated dose and dose-limiting toxicity in patients with unresectable pancreatic cancer.The recommended dose of S-1 for phase Ⅱ trials of chemoradiotherapy was determined as 80 mg/m2/day given on days 1-21 of a 28-day cycle.This phase Ⅱ study was conducted to further evaluate the efficacy and toxicity of radiotherapy combined with S-1.Eligible patients had locally advanced and unresectable pancreatic cancer without distant metastases, an Eastern Cooperative Oncology Group performance status of 0-1, adequate organ and marrow functions, and no prior anticancer therapy.Patients initially received 4 weeks of chemoradiotherapy.S-1 was given orally at a dose of 80 mg/m2/day twice daily on days 1-21.Radiotherapy was delivered in fractions of 1.25 Gy twice daily, 5 days per week for 4 weeks (total dose: 50 Gy in 40 fractions).One month after the completion of chemoradiotherapy, S-1 was administered for 14 days followed by a 14-day rest period.This cycle was repeated as maintenance therapy until disease progression or unacceptable toxicity.Fifty patients were enrolled in this phase Ⅱ study.Median follow-up was 14.6 months (range 5.4-58.9 months).Forty-three patients (86%) completed the scheduled course of chemoradiotherapy.There was no treatmentrelated death or grade 4 toxicity.The major toxic effects were leukopenia and nausea.The objective tumor response according to the Response Eval.uation Criteria in Solid Tumors criteria was partial response in 15 patients (30%) (95% confidence interval (CI), 18-45%), stable disease in 23 (46%), and progressive disease in 12 (24%).Median progression-free survival and median overall survival were 6.7 months (95% CI, 4.7-11.2 months) and 14.3 months (95% CI, 10.8-20.8months), respectively.Survival rates at 1 and 2 years were 62 and 27%, respectively.Combination therapy with S-1 and radiation in patients with locally advanced and unresectable pancreatic cancer is considered a promising, well-tolerated regimen that can be recommended as an effective treatment for locally advanced pancreatic cancer.