title: Randomized, open-label, phase III study of a 28-day oral regimen of eniluracil plus fluorouracil versus intravenous fluorouracil plus leucovorin as first-line therapy in patients with metastatic/advanced colorectal cancer.
abstract: OBJECTIVE
  To compare the efficacy and tolerability of eniluracil (EU)/fluorouracil (5-FU) with that of 5-FU/leucovorin (LV) as first-line therapy for patients with metastatic/advanced colorectal cancer.
  
  
  METHODS
  This multicenter, randomized, open-label, phase III study (FUMA3008) conducted in the United States and Canada compared the safety and efficacy of EU/5-FU (11.5 mg/m(2)/1.15 mg/m(2) twice daily for 28 days every 35 days) with that of intravenous 5-FU/LV (425 mg/m(2)/20 mg/m(2) once daily for 5 days every 28 days) in patients with previously untreated metastatic colorectal cancer. Overall survival (OS) was the primary end point.
  
  
  RESULTS
  A total of 981 patients were randomized and 964 patients received treatment (485 EU/5FU, 479 5FU/LV). Survival for EU/5-FU was not statistically equivalent (but not statistically inferior) to that for 5-FU/LV (hazard ratio, 0.880; 95% confidence interval [CI], 0.75 to 1.03). Median duration of survival was 13.3 months in the EU/5-FU group and 14.5 months in the 5-FU/LV group. Median duration of progression-free survival for EU/5-FU was statistically inferior to that of the control group (20.0 weeks [95% CI, 19.1 to 20.9 weeks] v 22.7 weeks [95% CI, 18.3 to 24.6 weeks]; P =.01). Both treatments were well tolerated. Diarrhea was the most common nonhematologic toxicity in both groups; treatment-related grade 3 or 4 diarrhea occurred in 19% of patients treated with EU/5-FU and 16% of patients receiving 5-FU/LV (P =.354). Grade 3 or 4 granulocytopenia occurred in 5% of EU/5-FU patients and 47% of 5-FU/LV patients.
  
  
  CONCLUSIONS
  Safety profiles of both treatments were acceptable. Although antitumor activity was observed, EU/5-FU did not meet the protocol-specified statistical criteria for equivalence to 5-FU/LV in terms of OS.
authors.affiliation: Biological Sciences Division, University of Chicago, Chicago, IL 60637-1463, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Schilsky
authors.forename: Jeremey
authors.initials: J
authors.lastname: Levin
authors.forename: William H
authors.initials: WH
authors.lastname: West
authors.forename: Alfred
authors.initials: A
authors.lastname: Wong
authors.forename: Bruce
authors.initials: B
authors.lastname: Colwell
authors.forename: Michael P
authors.initials: MP
authors.lastname: Thirlwell
authors.forename: Rafat H
authors.initials: RH
authors.lastname: Ansari
authors.forename: William N
authors.initials: WN
authors.lastname: Bell
authors.forename: Robin L
authors.initials: RL
authors.lastname: White
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Yates
authors.forename: Paul V
authors.initials: PV
authors.lastname: McGuirt
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: C073482:eniluracil; D014498:Uracil; D002955:Leucovorin; D005472:Fluorouracil