title: Phase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer: European Organisation for Research and Treatment of Cancer Gastrointestinal Group Study 40986.
abstract: OBJECTIVE
  To demonstrate that adding irinotecan to a standard weekly schedule of high-dose, infusional fluorouracil (FU) and leucovorin (folinic acid [FA]) can prolong progression-free survival (PFS).
  
  
  METHODS
  Four hundred thirty patients with measurable or assessable metastatic colorectal cancer were randomly assigned to receive either FA 500 mg/m(2) as a 2-hour infusion and FU 2.6 g/m(2) by intravenous 24-hour infusion, both administered weekly for 6 weeks, followed by a 2-week rest (Arbeitsgemeinschaft für Internistische Onkologie [AIO] arm, n = 216), or a similar schedule but with FU 2.3 or 2.0 g/m(2) preceded by irinotecan 80 mg/m(2) administered over 30 minutes (experimental group, n = 214).
  
  
  RESULTS
  The median PFS time in the experimental group was 8.5 months (95% CI, 7.6 to 9.9 months) compared with 6.4 months (95% CI, 5.3 to 7.2 months) in the AIO arm (P < .0001). The median overall survival time was increased from 16.9 to 20.1 months (P = .2779). The objective response rate was 62.2% (95% CI, 55.0% to 69.5%) in the experimental group and 34.4% (95% CI, 27.5% to 41.3%) in the AIO arm (P < .0001).
  
  
  CONCLUSIONS
  The addition of irinotecan to the standard AIO FU/FA regimen was associated with a highly significant improvement in PFS and response rate and was well tolerated. The results of this study confirm that irinotecan in combination with high-dose infusional FU/FA is a reference first-line treatment.
authors.affiliation: Department of Internal Medicine, University of Dresden, Dresden. onkologie@klinikum-oldenburg.de
authors.forename: C-H
authors.initials: CH
authors.lastname: Köhne
authors.forename: E
authors.initials: E
authors.lastname: van Cutsem
authors.forename: J
authors.initials: J
authors.lastname: Wils
authors.forename: C
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: M
authors.initials: M
authors.lastname: El-Serafi
authors.forename: M P
authors.initials: MP
authors.lastname: Lutz
authors.forename: M
authors.initials: M
authors.lastname: Lorenz
authors.forename: P
authors.initials: P
authors.lastname: Reichardt
authors.forename: H
authors.initials: H
authors.lastname: Rückle-Lanz
authors.forename: N
authors.initials: N
authors.lastname: Frickhofen
authors.forename: R
authors.initials: R
authors.lastname: Fuchs
authors.forename: H-G
authors.initials: HG
authors.lastname: Mergenthaler
authors.forename: T
authors.initials: T
authors.lastname: Langenbuch
authors.forename: U
authors.initials: U
authors.lastname: Vanhoefer
authors.forename: P
authors.initials: P
authors.lastname: Rougier
authors.forename: R
authors.initials: R
authors.lastname: Voigtmann
authors.forename: L
authors.initials: L
authors.lastname: Müller
authors.forename: B
authors.initials: B
authors.lastname: Genicot
authors.forename: O
authors.initials: O
authors.lastname: Anak
authors.forename: B
authors.initials: B
authors.lastname: Nordlinger
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin