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

• Published in: BMC cancer 2004-01, Vol.4
• Main Authors: Kuehr, Thomas, Ruff, Paul, Rapoport, Bernardo L, Falk, Stephen, Daniel, Francis, Jacobs, Conrad, Davidson, Neville, Thaler, Josef, Boussard, Blandine, Carmichael, James
• Format: Article
• Language: English
• ISSN: 1471-2407
• DOI: 10.1186/1471-2407-4-36

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/m super(2), 30- to 90-minute intravenous infusion on day 1), immediately followed by folinic acid (20 mg/m super(2)/day) and 5-fluorouracil (425 mg/m super(2), 15-minute bolus infusion) days 1 to 5, every four weeks. Results: Diarrhoea was dose limiting at 300 mg/m super(2 )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/m super(2). 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.