Complete hepatic venous isolation and extracorporeal chemofiltration as treatment for human hepatocellular carcinoma: a phase I study.
BACKGROUND
We performed a phase I study of a novel system of complete hepatic venous isolation and extracorporeal chemofiltration in patients with unresectable hepatocellular carcinoma (HCC) to determine (a) whether systemic exposure to doxorubicin could be limited after high-dose hepatic arterial infusion (HAI), and (b) the hepatic maximum tolerated dose (MTD) of doxorubicin.


METHODS
Ten patients with biopsy-proven HCC were treated with 20-min HAI of doxorubicin (17 total treatments). Two patients were treated with doxorubicin 60 mg/m2, three patients were treated at 90 mg/m2, and five patients received 120 mg/m2. A newly developed dual-balloon vena cava catheter was advanced from the femoral vein, and the balloons were inflated to isolate and capture total hepatic venous outflow. The hepatic venous blood was pumped through extracorporeal carbon chemofilters before return of the blood to the systemic circulation.


RESULTS
Peak systemic doxorubicin levels were an average 85.6% lower than were peak prefilter levels (p < 0.01). Because all catheters were placed percutaneously and because the chemofiltration markedly limited systemic chemotherapy exposure, patients were discharged 1 day after 16 of the 17 treatments. The hepatic and systemic MTD of doxorubicin in this treatment protocol was 120 mg/m2.


CONCLUSIONS
This novel system of complete hepatic venous isolation and chemofiltration limits systemic chemotherapy toxicity and will allow use of higher doses of chemotherapeutic agents to treat HCC.
Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
S A
SA
Curley
R A
RA
Newman
T B
TB
Dougherty
G M
GM
Fuhrman
D L
DL
Stone
J A
JA
Mikolajek
S
S
Guercio
A
A
Guercio
C H
CH
Carrasco
M T
MT
Kuo
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000503:physiopathology / Q000628:therapy*; D002404:Catheterization; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000009:adverse effects / Q000379:methods*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D006439:Hemodynamics; D006440:Hemofiltration; D006503:Hepatic Veins / Q000503:physiopathology / Q000601:surgery*; D006801:Humans; D007261:Infusions, Intra-Arterial; D008102:Liver Circulation; D008113:Liver Neoplasms / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000453:epidemiology / Q000209:etiology; D013997:Time Factors; D016306:Vena Cava Filters
D004317:Doxorubicin