Pharmacokinetic (pk) and safety study of irinotecan (Ir) and capecitabine (Cp) administered on a weekly schedule

2061 Background: In vitro studies show synergy between Cp and Ir. Since both drugs are metabolized by carboxyl esterases (CE), the potential for competitive inhibition is possible. We conducted a study to identify a safe dose and potential drug-drug interactions of this combination. Methods: This was an open-label phase I dose escalation trial. Ir was given as a 30 min infusion on days 1 and 8, and Cp on days 1–14 of a 21 day cycle. Plasma for pk analyses was drawn on days 1 and 8, at 0, 15, 30, 45, 60, 90, 120, 240, 360 min, and 24 hr, for total CPT-11, SN-38, SN-38-glucuronide (G), and APC. Results: 47 patients (pt) - median age 60 (32–83) years; performance status 0–1 (96%); diagnoses- ovarian (10), breast (5), cervical (5), colorectal (10) and others (17) received 202 (median 4, range 1–18) cycles in 6 dose cohorts - Ir (mg/m2)/Cp (mg/m2/day in 2 divided doses) 75/1500, 85/1500, 85/1750, 100/1750, 100/2000, 115/2000. At the highest dose tested (115/2000), 1 of 3 pt developed grade (G) 4 neutropenia wi...