title: Single-agent irinotecan or FOLFIRI as second-line chemotherapy for advanced colorectal cancer; results of a randomised phase II study (DaVINCI) and meta-analysis [corrected].
abstract: BACKGROUND
  Second-line treatment with irinotecan for advanced or metastatic colorectal cancer prolongs survival. It is uncertain whether irinotecan is better administered with 5-fluorouracil or alone in patients previously treated with a fluoropyrimidine. We compared toxicity (particularly diarrhoea), quality of life, and efficacy of combination chemotherapy and irinotecan in these patients.
  
  
  METHODS
  In DaVINCI, a randomised phase II trial, patients with advanced colorectal cancer were randomly allocated to: Combination therapy (FOLFIRI), irinotecan (180 mg/m(2) IV over 90 min, day 1), 5-fluorouracil (400mg/m(2) IV bolus and 2400 mg/m(2) by 46-hour infusion from day 1) and folinic acid (20mg/m(2) IV bolus, day 1), 2-weekly; or Single-agent, irinotecan (350 mg/m(2) IV over 90 min), 3-weekly. Toxicity was evaluated every treatment cycle; QOL and response 6-weekly. Analysis was by intention to treat. The trial, amended from a larger factorial design, was terminated early due to slow recruitment. Results were also combined with other second-line irinotecan trials.
  
  
  RESULTS
  We randomised 44 patients to combination and 45 to single agent. Eight patients in the irinotecan arm and 4 in the combination arm had grade 3/4 diarrhoea (P=0.24). Treatment groups did not differ significantly in overall QOL changes, response rate or progression free or overall-survival. In a systematic review of 29 trials of second-line irinotecan-based treatment, single-agent irinotecan was associated with more diarrhoea and alopecia than the combination but efficacy was similar.
  
  
  CONCLUSIONS
  Combination treatment compared with single-agent irinotecan reduces alopecia and diarrhoea without compromising efficacy on clinical outcomes. Both regimens remain as reasonable treatment options.
  
  
  BACKGROUND
  Research grant (Pfizer).
authors.affiliation: Department of Medicine, Concord Hospital, Concord, Sydney, Australia. stephen.clarke@sydney.edu.au
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Clarke
authors.forename: Sonia
authors.initials: S
authors.lastname: Yip
authors.forename: Chris
authors.initials: C
authors.lastname: Brown
authors.forename: Guy A
authors.initials: GA
authors.lastname: van Hazel
authors.forename: David T
authors.initials: DT
authors.lastname: Ransom
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.forename: G Mark
authors.initials: GM
authors.lastname: Jeffrey
authors.forename: Niall C
authors.initials: NC
authors.lastname: Tebbutt
authors.forename: Martin
authors.initials: M
authors.lastname: Buck
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Lowenthal
authors.forename: Amy
authors.initials: A
authors.lastname: Boland
authors.forename: Val
authors.initials: V
authors.lastname: Gebski
authors.forename: John
authors.initials: J
authors.lastname: Zalcberg
authors.forename: R John
authors.initials: RJ
authors.lastname: Simes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000505:Alopecia / Q000139:chemically induced; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003967:Diarrhea / Q000139:chemically induced; 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; D009367:Neoplasm Staging; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin