Results of pharmacokinetic modulating chemotherapy in combination with hepatic arterial 5-fluorouracil infusion and oral UFT after resection of hepatic colorectal metastases.

Abstract

Pharmacokinetic modulating chemotherapy (PMC) is a new therapeutic concept in combination with continuous 5-fluorouracil (5-FU) infusion and UFT. UFT enhanced plasma 5-FU concentration and antitumor effects during 5-FU infusion. The authors report on their experiences with arterial 5-FU infusion and UFT after resection of hepatic colorectal secondaries. Fifty-eight patients were divided into two groups after hepatectomy. Group A, 30 patients, underwent hepatic arterial infusion (HAI) via implantable port system with perfusion 5-FU for 2 consecutive days per week at 600 mg/m(2)/day, and oral administration of UFT at 400 mg/day for 5-7 days per week, repeated 10 times, and Group B, 28 patients, underwent oral administration of UFT at 400 mg/day for 6 months. All the patients were managed at the outpatient clinic at Hyogo College of Medicine, and recurrence, survival, and toxicity were documented. Plasma 5-FU concentrations during chemotherapy were detected using high performance liquid chromatography. Maximum plasma concentrations of 5-FU in Group A reached 144.0 ng/mL and in Group B 58.7 ng/mL. Cumulative 5-year survival rate after hepatectomy in Group A was 59% and in Group B was 27%. (P = 0.00001) HAI-PMC drastically decreased hepatic recurrence (median hepatic recurrence free times were 34.2 months in Group A vs. 18.4 months in Group B; P = 0.00002). Grade 3 toxicity in Group A was found in 3 patients Pharmacokinetic modulating chemotherapy was designed as a uracil-related biochemical modulation. HAI-PMC significantly decreased hepatic recurrence after curative resection. This new chemotherapy concept significantly improved prognosis in patients with hepatic colorectal metastases.