• 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, and Australasian Gastro-Intestinal Trials Group.
• Department of Medicine, Concord Hospital, Concord, Sydney, Australia. stephen.clarke@sydney.edu.au
• Eur. J. Cancer. 2011 Aug 1; 47 (12): 1826-36.

BackgroundSecond-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.MethodsIn 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.FindingsWe 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.InterpretationCombination treatment compared with single-agent irinotecan reduces alopecia and diarrhoea without compromising efficacy on clinical outcomes. Both regimens remain as reasonable treatment options.FundingResearch grant (Pfizer).Copyright © 2011 Elsevier Ltd. All rights reserved.

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