title: Randomized multicenter phase II study comparing a combination of fluorouracil and folinic acid and alternating irinotecan and oxaliplatin with oxaliplatin and irinotecan in fluorouracil-pretreated metastatic colorectal cancer patients.
abstract: OBJECTIVE
  To assess antitumor activity and safety of two regimens in advanced colorectal cancer (CRC) patients with proven fluorouracil (5-FU) resistance in a randomized phase II study: 5-FU/folinic acid (FA) combined with alternating irinotecan (also called CPT-11) and oxaliplatin (FC/FO tritherapy), and an oxaliplatin/irinotecan (OC) combination.
  
  
  METHODS
  Sixty-two patients were treated: arm FC/FO (32 patients) received, every 4 weeks, FA 200 mg/m(2) followed by a 400-mg/m(2) 5-FU bolus injection, then a 600-mg/m(2) continuous infusion of 5-FU on days 1 and 2 every 2 weeks administered alternately with irinotecan (180 mg/m(2) on day 1) and oxaliplatin (85 mg/m(2) on day 15). Arm OC (30 patients) received oxaliplatin 85 mg/m(2) and irinotecan 200 mg/m(2) every 3 weeks.
  
  
  RESULTS
  In an intent-to-treat analysis, two partial responses lasting 10.7 and 16 months were observed with the tritherapy regimen, and seven (median duration, 11 months; range, 10.6 to 11.4 months) were observed with the bitherapy regimen. Median progression-free and overall survival times were 8.2 and 9.8 months, respectively, in the FC/FO arm and 8.5 and 12.3 months, respectively, in the OC arm. Main grade 3/4 toxicities were, respectively, neutropenia, 53% and 47%; febrile neutropenia, 13% and 3%; diarrhea, 19% and 10%; vomiting, 6% and 13%; and neurosensory toxicity, 3% and 3%. No treatment-related deaths occurred.
  
  
  CONCLUSIONS
  The every-3-weeks OC combination is safe and active in advanced 5-FU-resistant CRC patients. The lower activity data seen with the tritherapy regimen may be related to the lower dose intensities of irinotecan and oxaliplatin in this schedule.
authors.affiliation: Department of Digestive Oncology, Regional Cancer Center, Institut Bergonié, 229 cours de l'Argonne, 33076 Bordeaux Cedex, France. becouarn@bergonie.org
authors.forename: Y
authors.initials: Y
authors.lastname: Bécouarn
authors.forename: E
authors.initials: E
authors.lastname: Gamelin
authors.forename: B
authors.initials: B
authors.lastname: Coudert
authors.forename: S
authors.initials: S
authors.lastname: Négrier
authors.forename: J Y
authors.initials: JY
authors.lastname: Pierga
authors.forename: J L
authors.initials: JL
authors.lastname: Raoul
authors.forename: J
authors.initials: J
authors.lastname: Provençal
authors.forename: O
authors.initials: O
authors.lastname: Rixe
authors.forename: C
authors.initials: C
authors.lastname: Krisch
authors.forename: C
authors.initials: C
authors.lastname: Germa
authors.forename: M
authors.initials: M
authors.lastname: Bekradda
authors.forename: D
authors.initials: D
authors.lastname: Mignard
authors.forename: M
authors.initials: M
authors.lastname: Mousseau
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin