Single-agent irinotecan or FOLFIRI as second-line chemotherapy for advanced colorectal cancer; results of a randomised phase II study (DaVINCI) and meta-analysis
Clarke, SJ and Yip, S and Brown, C and van Hazel, GA and Ransom, DT and Goldstein, D and Jeffrey, GM and Tebbutt, NC and Buck, M and Lowenthal, RM and Boland, A and Gebski, V and Zalcberg, J and Simes, RJ, Australasian Gastro-Intestinal Trials Group, Single-agent irinotecan or FOLFIRI as second-line chemotherapy for advanced colorectal cancer; results of a randomised phase II study (DaVINCI) and meta-analysis, European Journal of Cancer, 47, (12) pp. 1826-1836. ISSN 0959-8049 (2011) [Refereed Article]
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 (400 mg/m(2) IV bolus and 2400 mg/m(2) by 46-hour infusion from day 1) and folinic acid (20 mg/m(2) 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.
Second-line chemotherapy, Colorectal cancer, Irinotecan, FOLFIRI, Randomised phase II trial