Increased doxorubicin levels in hepatic tumors with reduced systemic drug exposure achieved with complete hepatic venous isolation and extracorporeal chemofiltration

We evaluated a novel system of complete hepatic venous isolation and chemofiltration (CHVI-CF) to reduce systemic drug exposure following regional hepatic infusion of doxorubicin. Rabbits bearing hepatic VX-2 tumors were given doxorubicin via either hepatic arterial infusion (HAI) or portal venous infusion (PVI). A dualballoon vena cava catheter and extracorporeal chemofilter were used to capture and filter hepatic venous blood in experimental animals. Control animals received chemotherapy without hepatic venous isolation and chemofiltration. Following a 5-min HAI of doxorubicin (3 or 5 mg/kg), control and experimental animals had similar doxorubicin levels in their livers and VX-2 tumors, but experimental animals showed a significant reduction in doxorubicin levels in systemic plasma, heart, and kidney tissue as compared with control animals (P<0.01). HAI produced a 4-fold increase in doxorubicin levels in VX-2 tumors as compared with the drug levels obtained using PVI (P<0.01). A single HAI of 3 mg/kg doxorubicin in animals treated with CHVI-CF produced marked tumor necrosis at 7 and 14 days after treatment. By increasing the total body clearance of doxorubicin, this system will allow HAI of higher doses of drug in attempts to improve the antitumor response.