title: Effects of sorafenib combined with low-dose interferon therapy for advanced hepatocellular carcinoma: a pilot study.
abstract: BACKGROUND
  Sorafenib is a standard of care for advanced hepatocellular carcinoma (HCC). An in vitro study showed the synergistic effects of sorafenib and interferon for HCC. To clarify the efficacy, combination therapy with sorafenib and interferon was performed for patients with advanced HCC.
  
  
  METHODS
  Pegylated interferon α-2a was administered every 2 weeks for the initial 4 weeks. Subsequently, it was combined with sorafenib. We evaluated the anti-tumor effect and biomarkers during treatment period.
  
  
  RESULTS
  The subjects were 13 patients with advanced HCC complicated by hepatitis C virus (HCV)-related liver cirrhosis. A partial response, stable disease and progressive disease were noted in 4, 6, and 3 patients, respectively. The response rate, the disease control rate, the mean time to progression and the median survival time (MST) were 30.8 % (4/13), 76.9 % (10/13), 12.2 months, and 17.5 months, respectively. In 8 Child-Pugh class A and 5 Child-Pugh class B patients, the MST was 22.0 and 11.0 months, respectively (p = 0.001). In plasma vascular endothelial growth factor (VEGF), serum alpha-fetoprotein (AFP), AFP-L3, a protein induced by vitamin K absence or antagonist-II (PIVKA II), and hepatocyte growth factor (HGF), there was no pretreatment factor and no biomarker during the combination therapy to predict therapeutic effect in the present study.
  
  
  CONCLUSIONS
  The results of this study suggest that combination therapy with sorafenib and interferon could be effective and safe in advanced HCC patients with HCV-related liver cirrhosis.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamakari, Inzai, Chiba, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Itokawa
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamakari, Inzai, Chiba, Japan. momogachi@yahoo.co.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Atsukawa
authors.affiliation: Core Research Facilities for Basic Science, Research Center for Medical Sciences, Jikei University, School of Medicine, Tokyo, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsubota
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamakari, Inzai, Chiba, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Okubo
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamakari, Inzai, Chiba, Japan.
authors.forename: Taeang
authors.initials: T
authors.lastname: Arai
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamakari, Inzai, Chiba, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Nakagawa
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamakari, Inzai, Chiba, Japan.
authors.forename: Chisa
authors.initials: C
authors.lastname: Kondo
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamakari, Inzai, Chiba, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Iwakiri
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D008103:Liver Cirrhosis / Q000150:complications / Q000821:virology; D008113:Liver Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011498:Protein Precursors / Q000097:blood; D011516:Prothrombin; D011994:Recombinant Proteins / Q000008:administration & dosage; D000077157:Sorafenib; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D016898:Interferon-alpha; D010671:Phenylurea Compounds; D011498:Protein Precursors; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D000509:alpha-Fetoproteins; D009536:Niacinamide; D011092:Polyethylene Glycols; C008208:acarboxyprothrombin; D017228:Hepatocyte Growth Factor; D011516:Prothrombin; D000077157:Sorafenib; C100416:peginterferon alfa-2a
keywords: Hepatocellular carcinoma; Pegylated interferon; Sorafenib; Vascular endothelial growth factor; α-Fetoprotein