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 c hemofiltration (CHVI-CF) to reduce systemic drug exposure following re gional hepatic infusion of doxorubicin. Rabbits bearing hepatic VX-2 t umors were given doxorubicin via either hepatic arterial infusion (HAI ) or portal venous infusion (PVI). A dual-balloon vena cava catheter a nd extracorporeal chemofilter were used to capture and filter hepatic venous blood in experimental animals. Control animals received chemoth erapy without hepatic venous isolation and chemofiltration. Following a 5-min HAI of doxorubicin (3 or 5 mg/kg), control and experimental an imals 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 doxorubi cin levels in VX-2 tumors as compared with the drug levels obtained us ing PVI (P < 0.01). A single HAI of 3 mg/kg doxorubicin in animals tre ated with CHVI-CF produced marked tumor necrosis at 7 and 14 days afte r treatment. By increasing the total body clearance of doxorubicin, th is system will allow HAI of higher doses of drug in attempts to improv e the antitumor response.