title: Hepatic arterial infusion chemotherapy with complete hepatic venous isolation and extracorporeal chemofiltration: a feasibility study of a novel system.
abstract: When chemotherapeutic drugs with low liver extraction are used for hepatic arterial infusion (HAI), dosage limits are usually determined by systemic rather than hepatic toxicity. If such agents could be administered by HAI at dosages limited by hepatic toxicity, regional drug exposure and therapeutic efficacy might be significantly enhanced. We report herein a novel system that achieves complete hepatic venous isolation using a dual-balloon vena cava catheter that can be inserted percutaneously. This catheter is connected to a carbon filter in an extracorporeal venous bypass circuit to recover drug that is not absorbed by the liver after HAI. The hemodynamic response to this system was evaluated in six pigs. When the animals were placed on the extracorporeal circuit, we observed a 22% decrease in cardiac output that was well tolerated without significant change in blood pressure. When the filter was incorporated into the circuit, cardiac output was significantly reduced (50%); however, continuous infusion of phenylephrine rapidly normalized blood pressure, heart rate, cardiac output, and left ventricular filling pressures. Initial testing of chemofiltration efficacy was performed in four of the six animals, the remaining two animals being used only to assess hemodynamic response. One each of the four tested animals received either doxorubicin (3 or 9 mg/kg), mitomycin C (1 mg/kg), or cisplatin (1 mg/kg) by HAI. The filter removed over 90% of hepatic venous doxorubicin and mitomycin C and 65% of hepatic venous cisplatin. This feasibility study confirms that hepatic venous isolation with chemofiltration can significantly reduce systemic exposure to high-dose chemotherapeutic agents given by HAI.
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 R
authors.initials: DR
authors.lastname: Byrd
authors.forename: R A
authors.initials: RA
authors.lastname: Newman
authors.forename: C H
authors.initials: CH
authors.lastname: Carrasco
authors.forename: D
authors.initials: D
authors.lastname: Cromeens
authors.forename: H J
authors.initials: HJ
authors.lastname: Ellis
authors.forename: J
authors.initials: J
authors.lastname: Chase
authors.forename: T
authors.initials: T
authors.lastname: Dougherty
authors.forename: K
authors.initials: K
authors.lastname: Wright
authors.forename: W
authors.initials: W
authors.lastname: Bodden
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002405:Catheterization, Central Venous; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D005112:Extracorporeal Circulation; D005240:Feasibility Studies; D006439:Hemodynamics / Q000502:physiology; D006440:Hemofiltration / Q000379:methods*; D006499:Hepatic Artery / Q000502:physiology*; D006503:Hepatic Veins / Q000502:physiology*; D007261:Infusions, Intra-Arterial; D008102:Liver Circulation / Q000502:physiology; D016685:Mitomycin / Q000008:administration & dosage; D013552:Swine
chemical_list: D000970:Antineoplastic Agents; D016685:Mitomycin; D004317:Doxorubicin; D002945:Cisplatin