High-dose mitomycin C in isolated hyperthermic liver perfusion for unresectable liver metastases

In order to reduce systemic side effects and increase intrahepatic mitomyci n C (MMC) concentrations, isolated hyperthermic liver perfusion (IHLP) has been performed using MMC. This article describes the pharmacokinetics of MM C in IHLP and presents our clinical experience with its use in six patients suffering from unresectable liver metastases. Primary tumors consisted of colorectal carcinomas in three cases, breast cancer in two, and a choroidal melanoma in one. Dosages of MMC varied between 0.5 and 1.0 mg MMC/kg body weight. MMC was added as a bolus directly into the extracorporeal circuit. Intrahepatic temperature was elevated to 40.0-41.0 degrees C by hyperthermi c perfusion. MMC concentrations were measured in peripheral blood (preperfu sion, then at 5, 30, and 55 min during perfusion, and finally at 5 and 60 m in and 6 and 24 h after perfusion) and in recirculating perfusate (5, 30, a nd 55 min). While markedly elevated MMC concentrations (maximum 6290 ng/mL) were found in the liver perfusate, systemic concentrations remained low (m aximum 45 ng/mL), indicating no considerable leakage. MMC concentrations in the perfusate constantly decreased during perfusion. After rinsing with 15 00 mL saline, a mean concentration of 52.5 +/- 33 ng MMC/mL was measured in the washout from 5 patients. In 1 patient with a colorectal carcinoma, MMC concentrations in the perfusion medium were 10-fold and in the plasma 2-fo ld higher than in the other patients. This high MMC concentration caused se vere intrahepatic vascular damage and finally led to the patient's death. I n conclusion, IHLP and intrahepatic perfusion with MMC resulted in a high r esponse of hepatic tumors. Systemic exposure of MMC can be reduced effectiv ely by isolated perfusion. However, hepatic toxicity of MMC must be conside red.