Randomized Multicenter Phase II Trial of Two Different Schedules of Irinotecan Combined with Capecitabine as First-Line Treatment in Metastatic Colorectal Carcinoma

BACKGROUND. The aim of the current randomized Phase II study was to investigate the efficacy and safety of capecitabine combined with irinotecan as first-line treatment in metastatic colorectal carcinoma (CRC). METHODS. A total of 140 patients received capecitabine at a dose of 1250 mg/m² twice daily on Days 2-15 and irinotecan at a dose of either 300 mg/m² on Day 1 (Arm A) or 150 mg/m² on Days 1 and 8 (Arm B) every 3 weeks. During the course of the study, enrollment was continued using lower doses of capecitabine (1000 mg/m² twice daily) and irinotecan (Arm A: 240 mg/m²; Arm B: 120 mg/m²) to improve the safety profile of the combinations. RESULTS. Efficacy was evaluable in 134 patients (68 in Arm A, 66 in Arm B). Objective responses were observed in 46% of the patients (8% complete response [CR]), including 47% in Arm A (9% CR; 38% partial response [PR]) and 44% in Arm B (8% CR; 36% PR). The median progression-free survival was 8.3 months in Arm A and 7.6 months in Arm B. Among the first 52 patients treated with the higher doses, the most frequent Grade 3-4 adverse event was diarrhea (27%). The lower doses adopted in the subsequent 88 patients led to better diarrhea control, particularly in Arm A, and significant reductions in the incidence of all-grade hand-foot syndrome and abdominal pain. CONCLUSIONS. The capecitabine and irinotecan combination was a highly active first-line therapy in metastatic CRC. An acceptable safety profile was observed after dose reduction, particularly when irinotecan was administered on 1 day.