title: Increased doxorubicin levels in hepatic tumors with reduced systemic drug exposure achieved with complete hepatic venous isolation and extracorporeal chemofiltration.
abstract: 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 dual-balloon 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.
authors.affiliation: Department of General Surgery, University of Texas M.D. Anderson Cancer Center, Houston 77030.
authors.forename: S A
authors.initials: SA
authors.lastname: Curley
authors.forename: D L
authors.initials: DL
authors.lastname: Stone
authors.forename: G M
authors.initials: GM
authors.lastname: Fuhrman
authors.forename: D C
authors.initials: DC
authors.lastname: Hohn
authors.forename: Z H
authors.initials: ZH
authors.lastname: Siddik
authors.forename: R A
authors.initials: RA
authors.lastname: Newman
mesh_terms: D000818:Animals; D002404:Catheterization; D010478:Chemotherapy, Cancer, Regional Perfusion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D005374:Filtration; D006499:Hepatic Artery; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D011169:Portal Vein; D011817:Rabbits; D014682:Vena Cava, Inferior
chemical_list: D004317:Doxorubicin