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BMC Cancer
Published in: BMC Cancer 1/2004

Open Access 01-12-2004 | Research article

Phase I/II study of first-line irinotecan combined with 5-fluorouracil and folinic acid Mayo Clinic schedule in patients with advanced colorectal cancer

Authors: Thomas Kuehr, Paul Ruff, Bernardo L Rapoport, Stephen Falk, Francis Daniel, Conrad Jacobs, Neville Davidson, Josef Thaler, Blandine Boussard, James Carmichael

Published in: BMC Cancer | Issue 1/2004

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Abstract

Background

This multicentre phase I/II study was designed to determine the maximum tolerated dose of irinotecan when combined with 5-fluorouracil and folinic acid according to the Mayo Clinic schedule and to evaluate the activity of this combination as first-line therapy in patients with advanced colorectal cancer.

Methods

Sixty-three patients received irinotecan (250 or 300 mg/m2, 30- to 90-minute intravenous infusion on day 1), immediately followed by folinic acid (20 mg/m2/day) and 5-fluorouracil (425 mg/m2, 15-minute bolus infusion) days 1 to 5, every four weeks.

Results

Diarrhoea was dose limiting at 300 mg/m2 irinotecan in combination with 5-fluorouracil and folinic acid, and this was determined to be the maximum tolerated dose. Grade 3–4 neutropenia was the most frequently reported toxicity. The recommended dose of irinotecan for the phase II part of the study was 250 mg/m2. The response rate for the evaluable patient population was 36% (13/36), and 44% (16 patients) had stable disease (including 19% of minor response). For the intention-to-treat population, the response rate was 29% (14/49) and 35% (17 patients) stable disease (including 14% of minor response). The median time to progression was 7.0 months and the median survival was 12.0 months. Grade 3–4 non-haematological drug-related toxicities included delayed diarrhoea, stomatitis, fatigue, and nausea/vomiting. There were three deaths due to septic shock that were possibly or probably treatment-related.

Conclusions

This regimen of irinotecan in combination with the Mayo Clinic schedule of bolus 5-fluorouracil/folinic acid every four weeks showed activity as first-line therapy in patients with advanced colorectal cancer. In keeping with other published results of studies using bolus 5-fluorouracil combined with irinotecan, the use of this regimen is limited by a relatively high rate of grade 3–4 neutropenia, and the combination of irinotecan and infusional 5-fluorouracil / folinic acid should remain the regimen of first choice.
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Metadata
Title
Phase I/II study of first-line irinotecan combined with 5-fluorouracil and folinic acid Mayo Clinic schedule in patients with advanced colorectal cancer
Authors
Thomas Kuehr
Paul Ruff
Bernardo L Rapoport
Stephen Falk
Francis Daniel
Conrad Jacobs
Neville Davidson
Josef Thaler
Blandine Boussard
James Carmichael
Publication date
01-12-2004
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2004
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-4-36

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