title: Pilot study of combination chemotherapy of S-1, a novel oral DPD inhibitor, and interferon-alpha for advanced hepatocellular carcinoma with extrahepatic metastasis.
abstract: BACKGROUND
  To the authors' knowledge, there is no effective therapy for extrahepatic metastasis of hepatocellular carcinoma (HCC). In a pilot study, the results of combination therapy of S-1, a novel oral dehydropyrimidine dehydrogenase (DPD) inhibitor, and interferon-alpha (IFN-alpha) are reported for HCC patients with extrahepatic metastasis.
  
  
  METHODS
  Twelve patients with extrahepatic metastasis of HCC were enrolled in the pilot study. S-1 was administered orally at a dose based on body surface area, twice daily after a meal, for 4 weeks. IFN-alpha was injected subcutaneously on Days 1, 3, and 5 of each week. One course consisted of consecutive administration for 28 days followed by 14 days rest.
  
  
  RESULTS
  An objective response was observed in 3 (25%) of 12 patients. The overall 1-year survival rate was 61.7%. Grade 3 leukocytopenia was observed in 1 patient (8.3%). No severe toxicity or treatment-related deaths were observed.
  
  
  CONCLUSIONS
  The combination therapy of S-1 and IFN-alpha appears to be highly efficacious, with low toxicity in patients with extrahepatic metastases of HCC. The combination chemotherapy of oral S-1 and subcutaneous IFN-alpha is a potentially promising treatment strategy for advanced HCC with extrahepatic metastasis.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.forename: Shigeru
authors.initials: S
authors.lastname: Marubashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyamoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takeda
authors.forename: Shogo
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wada
authors.forename: Takehiro
authors.initials: T
authors.lastname: Noda
authors.forename: Keizo
authors.initials: K
authors.lastname: Dono
authors.forename: Koji
authors.initials: K
authors.lastname: Umeshita
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000556:secondary; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000037:antagonists & inhibitors*; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage*; D007970:Leukopenia / Q000139:chemically induced; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage*; D010865:Pilot Projects; D012074:Remission Induction; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage*; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D007155:Immunologic Factors; D016898:Interferon-alpha; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D042943:Dihydrouracil Dehydrogenase (NADP)