title: Updated efficacy and toxicity analysis of irinotecan and oxaliplatin (IROX) : intergroup trial N9741 in first-line treatment of metastatic colorectal cancer.
abstract: BACKGROUND
  Efficacy and toxicity of oxaliplatin (Eloxatin; Sanofi-Aventis, Paris, France) combined with irinotecan (IROX) were examined in 383 patients enrolled on the IROX arm of Intergroup Study N9741.
  
  
  METHODS
  This IROX regimen was oxaliplatin 85 mg/m(2) and irinotecan 200 mg/m(2) administered every 3 weeks. The relation between adverse events on IROX to selected characteristics was analyzed. Time to progression (TTP), response rate, and overall survival for patients treated with IROX compared with patients treated with oxaliplatin with 5- fluorouracil (FOLFOX) were updated in this article.
  
  
  RESULTS
  Grade >or=3 gastrointestinal and hematologic toxicities were common with 39% patients experiencing neutropenia, 28% diarrhea, and 21% vomiting. Patients ages >70 years experienced higher rates of grade >or=3 toxicity, with significantly higher rates of grade >or=3 hematologic toxicities (P = .02). Long-term toxicity was uncommon, and nearly all cases of grade >or=3 neurotoxicity resolved within 10 months. Fifty-two percent of patients required dose reductions for adverse events, and 26% experienced 119 hospitalizations related to complications of treatment or their disease, with 5 treatment-related deaths. This analysis confirmed prior findings that FOLFOX is superior to IROX in terms of response rate (43% vs 36%, p = 0.002), TTP (9.2 months vs 6.7 months, P < .0001), and overall survival (19.5 months vs 17.3 months, P = .0001).
  
  
  CONCLUSIONS
  IROX was found to be less active than FOLFOX but with a similar toxicity profile except in patients ages >70 years. Although IROX may be considered in patients intolerant of 5-FU or in patients known to have a dihydropyrimidine dehydrogenase (DPD) deficiency, it should be used with caution in older patients.
authors.affiliation: Division of Medical Oncology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Ashley
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sargent
authors.forename: Steven R
authors.initials: SR
authors.lastname: Alberts
authors.forename: Axel
authors.initials: A
authors.lastname: Grothey
authors.forename: Megan E
authors.initials: ME
authors.lastname: Campbell
authors.forename: Roscoe F
authors.initials: RF
authors.lastname: Morton
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramanathan
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Williamson
authors.forename: Brian P
authors.initials: BP
authors.lastname: Findlay
authors.forename: Henry C
authors.initials: HC
authors.lastname: Pitot
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin