title: Semimonthly versus monthly regimen of fluorouracil and leucovorin administered for 24 or 36 weeks as adjuvant therapy in stage II and III colon cancer: results of a randomized trial.
abstract: OBJECTIVE
  This randomized, 2 x 2 factorial study compared a semimonthly (LVFU2) with a monthly (FULV) regimen of fluorouracil and leucovorin and 24 versus 36 weeks of each regimen as adjuvant treatment of patients with stage II (Dukes' B2) and III (Dukes' C) colon cancer.
  
  
  METHODS
  LVFU2 was administered semi-monthly for 2 consecutive days as dl- or l-leucovorin (200 or 100 mg/m2, respectively) as a 2-hour infusion, followed by a 400 mg/m2 FU bolus and 600 mg/m2 of FU as a 22-hour continuous infusion. FULV was administered monthly for 5 consecutive days as a 15-minute infusion of dl- or l-leucovorin, followed by 400 mg/m2 of FU as a 15-minute infusion.
  
  
  RESULTS
  A total of 905 patients were randomly assigned. The median follow-up was 41 months. Disease-free survival was similar between the LVFU2 and FULV groups (127 v 124 events; hazard ratio [HR] = 1.04; P =.74) and between 24 and 36 weeks of therapy (128 v 123 events; HR = 0.94; P =.63). Analysis of overall survival showed a slight excess in the number of deaths in LVFU2 compared with FULV (73 v 59), but this difference was not statistically significant (HR = 1.26; 95% confidence interval, 0.90 to 1.78; P =.18). The most commonly observed grade 3 to 4 toxicities were neutropenia, diarrhea, and mucositis. Toxicities were significantly lower in the LVFU2 group (all toxicities, P <.001).
  
  
  CONCLUSIONS
  Our data confirm that LVFU2 is less toxic than FULV. At a median follow-up of 41 months, no statistically significant difference could be detected in disease-free or overall survival between the treatment groups or treatment durations.
authors.affiliation: Hôpital Tenon, Groupe d'Etude et de Recherche Clinique en Oncologie Radioitherapie, Paris. thierry.andre@tnn.ap-hop-paris.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Andre
authors.forename: Philippe
authors.initials: P
authors.lastname: Colin
authors.forename: Christophe
authors.initials: C
authors.lastname: Louvet
authors.forename: Erik
authors.initials: E
authors.lastname: Gamelin
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouche
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Achille
authors.forename: Nicolas
authors.initials: N
authors.lastname: Colbert
authors.forename: Catherine
authors.initials: C
authors.lastname: Boaziz
authors.forename: Pascal
authors.initials: P
authors.lastname: Piedbois
authors.forename: Nicole
authors.initials: N
authors.lastname: Tubiana-Mathieu
authors.forename: Arnaud
authors.initials: A
authors.lastname: Boutan-Laroze
authors.forename: Michel
authors.initials: M
authors.lastname: Flesch
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
authors.forename: Aimery
authors.initials: A
authors.lastname: de Gramont
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D002955:Leucovorin; D005472:Fluorouracil