Rofecoxib associated with weekly irinotecan and infusional 5-fluorouracil as second-line treatment for metastatic colorectal cancer

3686 Background:We performed this Phase I –II study to determine the feasibility and activity of a “methronomic” schedule of chemotherapy with weekly irinotecan (CPT 11) and 5-fluorouracil (5-FU) by continuos infusion associated with a selective inhibitor of cyclooxygenase-2 (COX-2) as second-line therapy for advanced colorectal cancer. Methods:The patients (pts) had metastatic disease progressing after an oxaliplatin-based chemotherapy, age ≥ 18 to ≤ 75 years, good performance status and measurable lesions. A cycle of treatment consisted of two phases: induction (weeks 1 to 5), with rofecoxib at the oral dose of 50 mg/day combined with intravenous weekly CPT-11 on days 1–8-15–22 and infusional 5-FU at the dose of 200 mg/m2/day for 5 weeks, and maintenance (weeks 6 to 8) with rofecoxib alone. The starting dose of CPT-11 was of 87.5 mg/m2, further dose escalations were by increments of 12.5 mg/m2 per level up to 125 mg/m2. Results: Fifteen pts have been enrolled in the Phase I study. The dose limiting toxi...