Two arms, phase 3 study of irinotecan plus S1 versus S1 alone in previously treated patients with recurrent or metastatic esophageal cancer. 240 Patients will be enrolled in this trial. The primary objective of this study is to determine the PFS of the two arms. One arm is as follows: irinotecan 160 mg/m2 will be administered as an intravenous infusion over 60 minutes on Days 1, followed by S1 80mg to 120 mg per day on Days 1-10, every 14 days per cycle. The other arm is S1 80mg to 120 mg per day on Days 1-14, every 21 days per cycle.This study will also include the investigation of UGT1A1polymorphisms in the study population.