A Phase I dose-finding study using an innovative sequential biweekly schedule of irinotecan followed 24 hours later by capecitabine.
BACKGROUND: Irinotecan and capecitabine have a broad spectrum of activity in human malignancy and are synergistic in an animal model when irinotecan precedes capecitabine. PATIENTS AND METHODS: A Phase I design of the combination of irinotecan IV Day 1 with capecitabine on Days 2-8 every 2 weeks was evaluated in 27 adult patients with solid tumors. Two sequential schema were used: Arm A fixed the dose of irinotecan at 100 mg/m(2) and escalated capecitabine in cohorts, and arm B fixed the dose of capecitabine at 750 mg/m(2) PO BID and escalated the dosage of irinotecan. RESULTS: Neutropenia was dose limiting with nausea and diarrhea as the most common nonhematological toxicities. Significant interpatient variation in toxicity occurred despite uniform dosing. No Grade IV toxicities were encountered. Grade III toxicity occurred in first cycle in 15 percent (3/20) patients in arm A and 29 percent (2/7) of patients in arm B. All toxicities were reversible. Repetitive dosing was feasible with prolonged disease stabilization in 8 patients. CONCLUSIONS: The suggested Phase II dose of this combination and schedule is irinotecan 100 mg/m(2) and capecitabine 1000 mg/m(2) BID. Some patients tolerated a capecitabine dose as high as 1250 mg/m(2) BID.