Therapeutic efficacy of multimodal combination therapy using transcatheter arterial infusion of epirubicin and cisplatin, systemic infusion of 5-fluorouracil, and additional percutaneous ethanol injection for unresectable hepatocellular carcinoma.
OBJECTIVE
Previous studies have shown that a treatment regimen using epirubicin, cisplatin, and 5-fluorouracil (5-FU) (ECF) has a survival benefit for gastric cancer patients. Based on these results and the hypothesis that a combination modality has a better therapeutic advantage over a single mode of therapy, the efficacy of multimodal combination therapy using a transarterial infusion of epirubicin and cisplatin, systemic infusion of 5-FU, and additional percutaneous ethanol injection (PEI) for unresectable hepatocellular carcinoma (HCC) was investigated in this study in comparison with conventional transarterial chemoembolization (TACE).


METHODS
From July 1997 to September 1998, a total of 52 patients with unresectable HCC who underwent at least two cycles of transarterial chemotherapy were enrolled in this study. Among the 52 patients, 30 (ECF group) received a multimodal combination therapy comprising transarterial infusion of epirubicin (50 mg/m2) and cisplatin(60 mg/m2), systemic infusion of 5-FU (200 mg/m2), and additional PEI every 4 weeks, and the remaining 22(ADR group) received conventional TACE using Adriamycin (ADR, 50 mg) and Gelfoam every 8 weeks.


RESULTS
During the follow-up period (mean 13.8 +/ -8.5 months), the objective tumor response of the ECF group was significantly higher than that of the ADR group (53.3 vs 22.7%, P=0.044). The median survival time was 13.5 months for the ECF group and 10.5 months for the ADR group (P=0.026). The cumulative survival rates at 6, 12, 18, and 24 months,respectively, were 90, 57, 27, and 17% for the ECF group and 73, 37, 7, and 0% for the ADR group. Uni-variate analysis showed five prognostic factors including tumor number, tumor morphology, portal vein thrombosis, Child-Pugh classification, and tumor response. With multivariate analysis, portal vein thrombosis and tumor response were identified as the two independent f actors for survival. No serious adverse effect was observed in the ECF group, while there was a higher tendency for hepatic complications in the ADR group.


CONCLUSIONS
Combination therapy comprising transarterial infusion of epirubicin and cisplatin, systemic infusion of 5-FU, and additional PEI appears to be feasible and promising as a multimodal approach for unresectable HCC. Furthermore, it may provide a survival benefit for patients with more advanced disease.
Jang
Jeong Won
JW
Department of Internal Medicine, College of Medicine, WHO Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul, South Korea.
Park
Young Min
YM
Bae
Si Hyun
SH
Choi
Jong Young
JY
Yoon
Seung Kew
SK
Chang
U Im
UI
Nam
Soon Woo
SW
Kim
Boo Sung
BS
D000279:Administration, Cutaneous; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D000431:Ethanol / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007269:Injections, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies
D000431:Ethanol; D015251:Epirubicin; D002945:Cisplatin; D005472:Fluorouracil