Single-agent irinotecan or FOLFIRI as second-line chemotherapy for advanced colorectal cancer; results of a randomised phase II study (DaVINCI) and meta-analysis

Stephen J. Clarke, Sonia Yip, Chris Brown, Guy A. Van Hazel, David T. Ransom, David Goldstein, G. Mark Jeffrey, Niall C. Tebbutt, Martin Buck, Raymond M. Lowenthal, Amy Boland, Val Gebski, John Zalcberg, R. John Simes

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17 Citations (Scopus)


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/m2 IV over 90 min, day 1), 5-fluorouracil (400 mg/m2 IV bolus and 2400 mg/m2 by 46-hour infusion from day 1) and folinic acid (20 mg/m2 IV bolus, day 1), 2-weekly; or Single-agent, irinotecan (350 mg/m2 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. Findings: 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. Interpretation: Combination treatment compared with single-agent irinotecan reduces alopecia and diarrhoea without compromising efficacy on clinical outcomes. Both regimens remain as reasonable treatment options. Funding: Research grant (Pfizer).

Original languageEnglish
Pages (from-to)1826-1836
Number of pages11
JournalEuropean Journal of Cancer
Issue number12
Publication statusPublished - 1 Aug 2011
Externally publishedYes


  • Colorectal cancer
  • Irinotecan
  • Randomised phase II trial
  • Second-line chemotherapy

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