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

• Published in: BMC cancer Vol. 4; no. 1; p. 36
• Main Authors: Kuehr, Thomas, Ruff, Paul, Rapoport, Bernardo L, Falk, Stephen, Daniel, Francis, Jacobs, Conrad, Davidson, Neville, Thaler, Josef, Boussard, Blandine, Carmichael, James
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 16.07.2004; BioMed Central; BMC
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - mortality; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Camptothecin - administration & dosage; Camptothecin - analogs & derivatives; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - mortality; Diarrhea - chemically induced; Fatigue - chemically induced; Female; Fluorouracil - administration & dosage; Hematologic Diseases - chemically induced; Humans; Irinotecan; Leucovorin - administration & dosage; Male; Maximum Tolerated Dose; Middle Aged; Nausea - chemically induced; Shock, Septic - chemically induced; Stomatitis - chemically induced; Survival Rate
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-4-36

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. 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. 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. 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.