title: A systematic review of FOLFOXIRI chemotherapy for the first-line treatment of metastatic colorectal cancer: improved efficacy at the cost of increased toxicity.
abstract: OBJECTIVE
  The simultaneous administration of irinotecan, 5-fluorouracil, folinic acid and oxaliplatin (FOLFOXIRI) has been compared with standard 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) in randomized trials in metastatic colorectal cancer patients. A superior efficacy of FOLFOXIRI has been reported by some authors, but others have failed to show any differences and do not recommend its use because of greater cost and toxicity. We performed a systematic review of the literature to analyse efficacy and toxicity of FOLFOXIRI.
  
  
  METHODS
  Odds ratios (OR) with 95% confidence intervals (CI) were used to analyse dichotomous variables. Hazard ratios (HR) for progression and death were combined with an inverse variance method based on logarithmic conversion. A fixed-effect model and Mantel-Haenszel's method were used. Heterogeneity was tested with Cochrane's Q test and I(2) test.
  
  
  RESULTS
  A significant increase in response rate (OR 2.04; P < 0.01) was associated with treatment by FOLFOXIRI and a benefit was also shown by the HR for progression (HR 0.72; P < 0.01) and death (HR 0.71; P < 0.01). Analysis for toxicity found a significant increase associated with FOLFOXIRI except for anaemia, fatigue and febrile neutropenia.
  
  
  CONCLUSIONS
  FOLFOXIRI confers significant benefit in progression-free survival, survival, response and R0 resection rates but is more toxic compared with FOLFIRI.
authors.affiliation: Oncology Unit, S. Giuseppe Hospital, Florence, Italy. iago2003@libero.it
authors.forename: F
authors.initials: F
authors.lastname: Montagnani
authors.forename: A
authors.initials: A
authors.lastname: Chiriatti
authors.forename: G
authors.initials: G
authors.lastname: Turrisi
authors.forename: G
authors.initials: G
authors.lastname: Francini
authors.forename: G
authors.initials: G
authors.lastname: Fiorentini
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin