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Objective: We assessed the safety and efficacy of two regimens for patients with gastrointestinal cancers: continuous-infusion (CI) schedules of 5-Fluorouracil (5-Fu) plus a platinum (cisplatin or oxaiiplatin) with/or without paclitaxel (regimen A) versus Xeloda plus a platinum (cisplatin or oxaliplatin) with/or without paclitaxel for oral use (regimen B) in patients with gastrointestinal cancers. Methods: Between May 2003 and May 2005, 84 patients diagnosed in Jiangsu Cancer Hospital & Research Institute with locally advanced esophageal, gastric or colorectal cancer were registered. Regimen A and B consisted of either 5-Fu 0.375 C I days 1-14, every 28 days (n = 44), or Xeloda 1000 mg twice daily, days 1-14, every 28 days (n= 40). For both regimen A and B, Ⅳ cisplatin 25 mg/m2 was administered on day 1, 2 and 3 (or Oxaliplatin 75mg/m2 on day 1, 8 and 15) with or without paclitaxel 60-75 mg/m2 on day1, 8 and 15. Results: Patients receiving regimen B experienced significantly less stomatitis (P ＜ 0.05) and diarrhea (P ＜ 0.05), than those receiving regimen A. Prevalence of nausea/vomiting,alopecia, neutropenia, and hand-foot syndrome without significant difference between two regimens. No treatment related death occurred during study period. Regimen B demonstrates a similar, favorable safety profile in this study. Response rates and rates of clinical benefit for regimen A and B were 40.9%, 40.0% and 43.2%, 65.0% respectively. Conclusion: Based on its improved safety profile and improved rate of clinical benefit, Xeloda has the potential to replace CI 5-FU as an alternative treatment for patients with gastrointestinal cancers.