title: FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study.
abstract: OBJECTIVE
  In metastatic colorectal cancer, phase III studies have demonstrated the superiority of fluorouracil (FU) with leucovorin (LV) in combination with irinotecan or oxaliplatin over FU + LV alone. This phase III study investigated two sequences: folinic acid, FU, and irinotecan (FOLFIRI) followed by folinic acid, FU, and oxaliplatin (FOLFOX6; arm A), and FOLFOX6 followed by FOLFIRI (arm B).
  
  
  METHODS
  Previously untreated patients with assessable disease were randomly assigned to receive a 2-hour infusion of l-LV 200 mg/m(2) or dl-LV 400 mg/m(2) followed by a FU bolus 400 mg/m(2) and 46-hour infusion 2,400 to 3,000 mg/m(2) every 46 hours every 2 weeks, either with irinotecan 180 mg/m(2) or with oxaliplatin 100 mg/m(2) as a 2-hour infusion on day 1. At progression, irinotecan was replaced by oxaliplatin (arm A), or oxaliplatin by irinotecan (arm B).
  
  
  RESULTS
  Median survival was 21.5 months in 109 patients allocated to FOLFIRI then FOLFOX6 versus 20.6 months in 111 patients allocated to FOLFOX6 then FOLFIRI (P =.99). Median second progression-free survival (PFS) was 14.2 months in arm A versus 10.9 in arm B (P =.64). In first-line therapy, FOLFIRI achieved 56% response rate (RR) and 8.5 months median PFS, versus FOLFOX6 which achieved 54% RR and 8.0 months median PFS (P =.26). Second-line FOLFIRI achieved 4% RR and 2.5 months median PFS, versus FOLFOX6 which achieved 15% RR and 4.2 months PFS. In first-line therapy, National Cancer Institute Common Toxicity Criteria grade 3/4 mucositis, nausea/vomiting, and grade 2 alopecia were more frequent with FOLFIRI, and grade 3/4 neutropenia and neurosensory toxicity were more frequent with FOLFOX6.
  
  
  CONCLUSIONS
  Both sequences achieved a prolonged survival and similar efficacy. The toxicity profiles were different.
authors.affiliation: Hôpital Saint-Antoine, 184 Rue du Faubourg Saint-Antoine, 75571 Paris, Cedex 12, France. aimery.de-gramont@sat.ap-hop-paris.fr
authors.forename: Christophe
authors.initials: C
authors.lastname: Tournigand
authors.forename: Thierry
authors.initials: T
authors.lastname: André
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Achille
authors.forename: Gérard
authors.initials: G
authors.lastname: Lledo
authors.forename: Michel
authors.initials: M
authors.lastname: Flesh
authors.forename: Dominique
authors.initials: D
authors.lastname: Mery-Mignard
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Quinaux
authors.forename: Corinne
authors.initials: C
authors.lastname: Couteau
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
authors.forename: Gérard
authors.initials: G
authors.lastname: Ganem
authors.forename: Bruno
authors.initials: B
authors.lastname: Landi
authors.forename: Philippe
authors.initials: P
authors.lastname: Colin
authors.forename: Christophe
authors.initials: C
authors.lastname: Louvet
authors.forename: Aimery
authors.initials: A
authors.lastname: de Gramont
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016019:Survival Analysis
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin