Concurrent irinotecan, oxaliplatin and UFT in first-line treatment of metastatic colorectal cancer: a Phase I study

摘要

The feasibility of combining UFT plus leucovorin (LV) with alternating irinotecan and oxaliplatin was investigated in the first-line treatment of patients with advanced colorectal cancer. Twenty-five patients, median age 63 (range 24–79) years, World Health Organisation performance status 0–2 and median four marker lesions, received irinotecan 180?mg?m?2 on day 1, oxaliplatin 85–100?mg?m?2 on day 15 and UFT 200–300?mg?m?2 day?1 with LV 90?mg?day?1, days 1–21 of a 28-day cycle. Patients were treated in cohorts of three. At the highest dose (irinotecan 180?mg?m?2, oxaliplatin 100?mg?m?2 and UFT 300?mg?m?2 day?1), three of four patients experienced grade 3 toxicity. Diarrhoea, lethargy and vomiting were dose-limiting. Three of nine patients had grade 2 toxicities at the maximum tolerated dose (irinotecan 180?mg?m?2, oxaliplatin 100?mg?m?2 and UFT 250?mg?m?2 day?1). There were no grade 3 toxicities in the first month of therapy. The overall response rate was 71% in 21 evaluable patients; progression-free survival was 8.8 months. Alternating irinotecan and oxaliplatin plus UFT is an effective and well-tolerated first-line treatment for patients with advanced colorectal cancer. We recommend a dose of irinotecan 180?mg?m?2 on day 1, oxaliplatin 100?mg?m?2 on day 15 and UFT 250?mg?m?2 day?1 with LV 90?mg?day?1 on days 1–21 of a 28-day cycle for future studies.