Phase I/II study of irinotecan, UFT and leucovorin with hepatic arterial infusion using 5-FU in colorectal cancer patients with unresectable liver metastases

To evaluate the efficacy and tolerability of systemic chemotherapy with irinotecan (CPT-11), UFT and leucovorin (LV) combined with hepatic arterial infusion (HAI) consisting of 5-fluorouracil (5-FU) in colorectal cancer patients with unresectable liver metastases. Patients were treated concurrently with escalating doses of intravenous CPT-11 (100, 120, and 140 mg/m(2)) on day 1 of each 14-day treatment cycle, with oral UFT (300 mg/m(2) per day) and LV (75 mg/body per day) on days 1-7 of each cycle, and with HAI 5-FU (2,000 mg/week) on days 8-14 of each cycle. Twelve patients were enrolled in the phase I study. The maximum-tolerated dose was not reached. Consequently, the recommended dose of CPT-11 for the phase II study was determined to be 140 mg/m(2). Twenty-two patients were evaluated in the phase II study. Five patients experienced grade 3 neutropenia, two experienced grade 3 anorexia, two experienced nausea, and two experienced vomiting. An overall response was observed in 19 out of 22 patients (86.4%). The median progression-free survival period was 11.2 months, and the 3-year survival rate was 50.6%. Fourteen patients (63.6%) were ultimately able to undergo a complete liver resection. Chemotherapy with CPT-11 and UFT/LV combined with HAI yielded a high response rate and enabled a significant proportion of patients with initially unresectable liver metastases to undergo surgical resection. Further trials are warranted.