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Updated: Aug 2, 2026
Isolated Hepatic Perfusion as a Treatment for Liver Metastases of Uveal Melanoma
Published on: January 25, 2015
High-dose mitomycin C in isolated hyperthermic liver perfusion for unresectable liver metastases
K J Oldhafer1, M K Frerker, H Lang
1Department of Abdominal and Transplantation Surgery, Hannover Medical School, Germany.
Abstract:
In order to reduce systemic side effects and increase intrahepatic mitomycin C (MMC) concentrations, isolated hyperthermic liver perfusion (IHLP) has been performed using MMC. This article describes the pharmacokinetics of MMC 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 hyperthermic perfusion. MMC concentrations were measured in peripheral blood (preperfusion, then at 5, 30, and 55 min during perfusion, and finally at 5 and 60 min and 6 and 24 h after perfusion) and in recirculating perfusate (5, 30, and 55 min). While markedly elevated MMC concentrations (maximum 6290 ng/mL) were found in the liver perfusate, systemic concentrations remained low (maximum 45 ng/mL), indicating no considerable leakage. MMC concentrations in the perfusate constantly decreased during perfusion. After rinsing with 1500 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-fold higher than in the other patients. This high MMC concentration caused severe intrahepatic vascular damage and finally led to the patient's death. In conclusion, IHLP and intrahepatic perfusion with MMC resulted in a high response of hepatic tumors. Systemic exposure of MMC can be reduced effectively by isolated perfusion. However, hepatic toxicity of MMC must be considered.
Insights
Isolated hyperthermic liver perfusion (IHLP) with mitomycin C (MMC) effectively concentrates the drug in the liver while minimizing systemic exposure. However, careful monitoring is crucial due to potential hepatic toxicity.
Area of Science:
- Oncology
- Pharmacology
- Surgical Oncology
Background:
- Unresectable liver metastases present a significant treatment challenge.
- Systemic chemotherapy often leads to dose-limiting toxicities.
- Targeted delivery of chemotherapy to the liver can improve efficacy and reduce side effects.
Purpose of the Study:
- To evaluate the pharmacokinetics of mitomycin C (MMC) during isolated hyperthermic liver perfusion (IHLP).
- To assess the clinical efficacy and safety of IHLP with MMC for unresectable liver metastases.
- To determine the systemic exposure and intrahepatic concentration of MMC during IHLP.
Main Methods:
- Six patients with unresectable liver metastases underwent IHLP with MMC.
- MMC was administered as a bolus into the extracorporeal circuit.
- Intrahepatic temperature was maintained at 40.0-41.0°C.
- MMC concentrations were measured in peripheral blood and recirculating perfusate at various time points.
Main Results:
- Markedly elevated intrahepatic MMC concentrations (max 6290 ng/mL) were achieved with low systemic levels (max 45 ng/mL).
- MMC concentrations in the perfusate decreased during perfusion.
- One patient experienced severe intrahepatic vascular damage and mortality due to exceptionally high MMC concentrations.
Conclusions:
- IHLP with MMC demonstrates a high response rate in hepatic tumors.
- Isolated perfusion effectively reduces systemic exposure to MMC.
- Hepatic toxicity of MMC necessitates careful patient selection and monitoring during IHLP.
