A phase I study of irinotecan and 5'-DFUR in patients with metastatic colorectal cancer: With consideration of gene polymorphism

3630 Background: 5-Fluorouracil plus irinotecan (CPT-11) is standard 1st-line therapy in patients (pts) with metastatic colorectal cancer (MCRC). 5'-DFUR is a tumor-activated oral fluoropyrimidine. We conduct a phase I trial of CPT-11 and 5'-DFUR to determine the maximum tolerated dose (MTD) and toxicities of this regimen. However, detoxification of SN-38 (active form of CPT-11) is depending on UGT1A1 polymorphism. Here we report the results from a phase I study to determine the significance of UGT1A1 polymorphism on toxicity in pts with MCRC. Patients and methods: Eligibility criteria were as follows; histologically proven CRC with unresectable metastatic lesions, PS 0–2, age<75, adequate organ functions, and written informed consent. 5'-DFUR was administered orally (level 1 and 2; 600 mg/body, level 2b and 3; 800 mg/body) on 5 consecutive days with 2 days' rest for 12 weeks, and CPT-11 was infused (level 1, 2, 2b, and 3: 50, 70, 70, 100 mg/m2, respectively) on days 1, 15, 29, 43, 57, and 71. Dose limiti...