TY - JOUR
T1 - Single-agent irinotecan or FOLFIRI as second-line chemotherapy for advanced colorectal cancer; results of a randomised phase II study (DaVINCI) and meta-analysis
AU - Clarke, Stephen J.
AU - Yip, Sonia
AU - Brown, Chris
AU - Van Hazel, Guy A.
AU - Ransom, David T.
AU - Goldstein, David
AU - Jeffrey, G. Mark
AU - Tebbutt, Niall C.
AU - Buck, Martin
AU - Lowenthal, Raymond M.
AU - Boland, Amy
AU - Gebski, Val
AU - Zalcberg, John
AU - Simes, R. John
N1 - Funding Information:
Authors recruiting patients received per patient payments from the coordinating centre. DR received travel funding from Roche. DG received advisory board honoraria from Pfizer, Novartis, Roche and Merck and travel funding from Novartis and Pfizer. SY was a former employee of Novartis and previously held company shares. JZ received honoraria and research funding from Pfizer. The other authors declared no conflicts of interest.
Funding Information:
AGITG was the sponsor responsible for undertaking the DaVinci trial, and the NHMRC Clinical Trials Centre was the coordinating centre responsible for performing the trial under the auspices of AGITG. The trial was supported by an educational grant from Pfizer Australia Pty Ltd .
Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 2011/8/1
Y1 - 2011/8/1
N2 - 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).
AB - 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).
KW - Colorectal cancer
KW - FOLFIRI
KW - Irinotecan
KW - Randomised phase II trial
KW - Second-line chemotherapy
UR - http://www.scopus.com/inward/record.url?scp=80051544872&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2011.04.024
DO - 10.1016/j.ejca.2011.04.024
M3 - Article
C2 - 21665462
AN - SCOPUS:80051544872
VL - 47
SP - 1826
EP - 1836
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
IS - 12
ER -