title: Oral uracil/ftorafur (UFT) plus leucovorin as first-line chemotherapy and salvage therapy with weekly high-dose 5-fluorouracil/leucovorin for the treatment of metastatic colorectal cancer.
abstract: BACKGROUND
  The purpose of this study was to determine the efficacy and toxicity of uracil/ftorafur (UFT) plus oral leucovorin (LV) as first-line chemotherapy for patients with metastatic colorectal cancer and salvage chemotherapy with weekly high-dose 5-fluorouracil (5-FU)/LV 24 h infusion.
  
  
  METHODS
  Adult patients with no prior chemotherapy for metastatic diseases were enrolled to receive oral UFT 300 mg/m(2)/d plus LV 90 mg/d for 28 days. Treatment was given continuously for 28 days followed by a 7 day rest period from all treatment. For UFT failed patients, weekly 24 h infusion of 5-FU 2600 mg/m(2) plus LV 100 mg/m(2) was used as salvage therapy.
  
  
  RESULTS
  Fifty-one patients with metastatic colorectal cancer were enrolled in the study. The objective response rate was 29.5% [95% confidence interval (CI), 16.8-45.2%] among the 44 evaluable patients and 25.5% in the intent-to-treat population. The median survival for all 51 patients was 16.6 months. The median time to progression was 5.9 months. Diarrhea was the major adverse effect of UFT/LV that made patients reduce dosage. Grade 3 or 4 diarrhea developed in 13.7% of patients. Twenty-six patients were treated with weekly 24 h infusional 5-FU/LV as salvage therapy and only two patients responded.
  
  
  CONCLUSIONS
  Our results suggest that this 28 day schedule of UFT/LV regimen may offer a well-tolerated, full oral treatment option with efficacy that appears comparable to that of intravenous 5-FU/LV regimens. Parenteral 5-FU/LV as salvage therapy for UFT refractory patients is not recommended.
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine and Colorectal Section, Department of Surgery, Chang Gung Memorial Hospital, Taipei, Taiwan. tsyangss@ms27.hinet.net
authors.forename: Tsai-Shen
authors.initials: TS
authors.lastname: Yang
authors.forename: Jeng-Yi
authors.initials: JY
authors.lastname: Wang
authors.forename: Reiping
authors.initials: R
authors.lastname: Tang
authors.forename: Kuan-Cheng
authors.initials: KC
authors.lastname: Hsu
authors.forename: Jen-Shi
authors.initials: JS
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016879:Salvage Therapy; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; C096910:UFT(R) drug; D005641:Tegafur; D014498:Uracil; D002955:Leucovorin; D005472:Fluorouracil