title: 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.
abstract: 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.
authors.affiliation: Department of Internal Medicine, College of Medicine, WHO Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Jeong Won
authors.initials: JW
authors.lastname: Jang
authors.forename: Young Min
authors.initials: YM
authors.lastname: Park
authors.forename: Si Hyun
authors.initials: SH
authors.lastname: Bae
authors.forename: Jong Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Seung Kew
authors.initials: SK
authors.lastname: Yoon
authors.forename: U Im
authors.initials: UI
authors.lastname: Chang
authors.forename: Soon Woo
authors.initials: SW
authors.lastname: Nam
authors.forename: Boo Sung
authors.initials: BS
authors.lastname: Kim
mesh_terms: 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
chemical_list: D000431:Ethanol; D015251:Epirubicin; D002945:Cisplatin; D005472:Fluorouracil