Percutaneous hepatic vein isolation and high-dose hepatic arterial infusion chemotherapy for unresectable liver tumors.
OBJECTIVE
This prospective, nonrandomized trial evaluated a percutaneous isolated chemotherapy perfusion approach for treating advanced primary and metastatic liver tumors. Chemotherapy was administered via hepatic artery catheter and hepatic venous blood isolated by a novel percutaneous double-balloon inferior vena cava (IVC) catheter was passed through a detoxification/filtration cartridge in a venovenous bypass circuit.


METHODS
Among 23 patients enrolled onto the study, 58 procedures were performed on 21 patients. Twelve patients received dose escalations of fluorouracil (5-FU) (1,000 mg/m2 to 5,000 mg/m2), and nine received dose escalations of doxorubicin (50 mg/m2 to 120 mg/m2). Pharmacokinetic studies included drug accumulation in the liver, extraction by detoxification filters, systemic exposure, and alterations of half-life. Each patient received two treatments at 3-week intervals. Those showing stabilization or response received additional treatments.


RESULTS
There was a direct relationship between dose and peak concentration of drug entering the hepatic veins. The system functioned efficiently throughout the dose range, with extraction efficiencies ranging from 64% to 91% (P < .001). The hepatic vein drug levels showed a sixfold increase in 5-FU with dose escalation from 1,000 to 5,000 mg/m2, and a twofold increase in dox with dose escalation from 50 to 120 mg/m2 (P < .001, filter-mediated drug extraction). The treatments were accomplished with only an overnight hospital stay and no mortality. The common procedure-related toxicity was transient hypotension (grade I to II), due to catecholamine depletion by the filter. Dose-limiting toxicity (leukopenia) was observed in patients receiving 5-FU at a dose of 5,000 mg/m2 and doxorubicin at a dose of 120 mg/m2. Significant tumor response (> 95% reduction) was obtained in two patients receiving doxorubicin at 90 mg/m2 and 120 mg/m2.


CONCLUSIONS
The use of a double-balloon catheter to isolate and detoxify hepatic venous blood during intraarterial therapy is technically feasible, safe, and allows administration of large doses of intrahepatic chemotherapy at short intervals. This approach should allow new dose-intensification strategies to increase tumor responses in primary and metastatic liver tumors.
Ravikumar
T S
TS
Section of Surgical Oncology, Yale School of Medicine, New Haven, CT.
Pizzorno
G
G
Bodden
W
W
Marsh
J
J
Strair
R
R
Pollack
J
J
Hendler
R
R
Hanna
J
J
D'Andrea
E
E
D002759:Adenoma, Bile Duct / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002405:Catheterization, Central Venous / Q000009:adverse effects / Q000295:instrumentation; D004317:Doxorubicin / Q000008:administration & dosage; D005112:Extracorporeal Circulation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006503:Hepatic Veins; D006801:Humans; D007261:Infusions, Intra-Arterial / Q000295:instrumentation; D007902:Length of Stay; D007970:Leukopenia / Q000139:chemically induced; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013552:Swine; D016896:Treatment Outcome
D004317:Doxorubicin; D005472:Fluorouracil