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Single-agent irinotecan or 5-fluorouracil and leucovorin (FOLFIRI) as second-line chemotherapy for advanced colorectal cancer; results of a randomised phase II study (DaVINCI) and meta-analysis.

Author(s): Clarke SJ, Yip S, Brown C, van Hazel GA, Ransom DT, Goldstein D, Jeffrey GM, Tebbutt NC, Buck M, Lowenthal RM, Boland A, Gebski V, Zalcberg J, Simes RJ

Affiliation(s): Department of Medicine, Concord Hospital, Concord, Sydney, Australia. stephen.clarke@sydney.edu.au

Publication date & source: 2011-08, Eur J Cancer., 47(12):1826-36. Epub 2011 Jun 12.

Publication type: Clinical Trial, Phase II; Meta-Analysis; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

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. 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). Copyright (c) 2011 Elsevier Ltd. All rights reserved.

Page last updated: 2011-12-09

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