Intraperitoneal infusion of 5-FU in liver metastases from colorectal cancer

Intraperitoneal 5-fluorouracil (5-FU) was given to eight patients with unresectable colorectal liver cancer and to one patient after radical hepatectomy. A subcutaneous intraperitoneal access device was implanted, and treatment consisted of continuous infusion of 1,000 mg 5-FU/d for 5 days, repeated every 6 weeks. Evaluation of treatment was performed after every two cycles of therapy. A total of 32 infusion cycles were given. The mean steady-state concentration of 5-FU was 0.56 +/- 0.04 mumol/l (mean +/- SEM), and the total body clearance was 10.0 +/- 0.71/min mean +/- SEM). The levels of 5-FU in peripheral venous blood were stable and reproducible. When incubated in whole blood at 37 degrees C the concentration of 5-FU fell rapidly and after 2 h, only 22% of the starting level remained. When kept ice-cold, 5-FU samples were stable. Patient acceptance was excellent, and the therapy was free from complications except for slight abdominal discomfort, not enough to require alleviation by analgesic drugs. Computerized tomography (CT) scan showed stationary tumor volume after two cycles of therapy in four of eight patients who could be evaluated. It is concluded that continuous intraperitoneal infusion of 5-FU produces stable and reproducible levels of the drug in peripheral venous blood, that 5-FU is degraded by blood cells at 37 degrees C, that the use of a subcutaneous access device makes the delivery easy and safe, and that the efficacy of the therapy seems to be similar to that obtained with hepatic arterial infusion.