title: Systemic combination therapy of intravenous continuous 5-fluorouracil and subcutaneous pegylated interferon alfa-2a for advanced hepatocellular carcinoma.
abstract: BACKGROUND
  In Japan, sorafenib is now the first-line therapy for individuals with advanced hepatocellular carcinoma (HCC), but no other treatment is available for such patients. The aim of this study was to assess the efficacy and safety of combination therapy with systemic continuous intravenous infusion of 5-fluorouracil (5-FU) and subcutaneous peginterferon alfa-2a, which was used before sorafenib was introduced to Japan.
  
  
  METHODS
  Two hundred and twenty-three HCC patients, who were not amenable to curative surgery, percutaneous ablation, or transarterial chemoembolization (TACE), and for whom intraarterial chemotherapy was not indicated because of the presence of extrahepatic metastasis or stenosis of the common hepatic artery, received peginterferon alfa-2a (90 μg subcutaneously on days 1, 8, 15, and 22) and 5-FU (500 mg/day intravenously given continuously on days 1-5 and 8-12). We assessed their response to treatment and survival, and treatment safety.
  
  
  RESULTS
  The response rate was 9.4 % (including six patients with complete response) and the disease-control rate was 32.7 %. The median time to progression was 2.0 months. The overall median survival time was 6.5 months (Child-Pugh class A: 9.2 months vs. Child-Pugh class B: 2.8 months). In a multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status >0, Child-Pugh class B, and the presence of macroscopic vascular invasion were independent predictors of poor prognosis. The major grade 3-4 adverse events were leucopenia (13.9 %) and thrombocytopenia (5.8 %). No treatment-related deaths occurred.
  
  
  CONCLUSIONS
  This combination therapy was well tolerated and showed promising efficacy. Further studies are needed to establish the usefulness of this treatment.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Uchino
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Obi
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tateishi
authors.forename: Shinpei
authors.initials: S
authors.lastname: Sato
authors.forename: Miho
authors.initials: M
authors.lastname: Kanda
authors.forename: Takahisa
authors.initials: T
authors.lastname: Sato
authors.forename: Toru
authors.initials: T
authors.lastname: Arano
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Enooku
authors.forename: Eriko
authors.initials: E
authors.lastname: Goto
authors.forename: Ryota
authors.initials: R
authors.lastname: Masuzaki
authors.forename: Hayato
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Asaoka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kondo
authors.forename: Noriyo
authors.initials: N
authors.lastname: Yamashiki
authors.forename: Tadashi
authors.initials: T
authors.lastname: Goto
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Shiina
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Yoshida
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality; D015331:Cohort Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007564:Japan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a; D005472:Fluorouracil