title: Safety and effectiveness of sorafenib in Japanese patients with hepatocellular carcinoma in daily medical practice: interim analysis of a prospective postmarketing all-patient surveillance study.
abstract: BACKGROUND
  Sorafenib was approved for treatment of unresectable hepatocellular carcinoma (HCC) in Japan in 2009. A prospective postmarketing all-patient surveillance (PMS) study was requested by Japanese authorities to confirm safety and effectiveness of sorafenib in Japanese HCC population.
  
  
  METHODS
  Patients with unresectable HCC treated with sorafenib were followed up for 12 months. Data on patient demographic characteristics, treatment status, clinical outcome, and adverse events (AEs) were collected.
  
  
  RESULTS
  This interim analysis included 1109 and 1065 patients evaluable for safety and effectiveness, respectively. Most patients (83.4 %) received the recommended initial dose of 400 mg twice daily. After a follow-up of 12-months, 89.8 % had discontinued treatment, most because of AEs (44.5 %) or progression (33.8 %). The most common drug-related adverse events (DRAE) were hand-foot skin reaction (51.4 %), liver dysfunction (26.4 %), diarrhea (25.1 %), and hypertension (21.6 %). The median overall survival (OS) was 348 days [95 % confidence interval (CI) 299-389 days], and the median duration of treatment was 87 days (95 % CI 78-98 days). Multivariate analyses identified baseline prognostic factors for longer OS, including female sex, low Child-Pugh score, Eastern Cooperative Oncology Group performance status 0, tumor stage I/II/III, low aspartate aminotransferase level, high hemoglobin level, hepatitis C and history of surgical resection.
  
  
  CONCLUSIONS
  In general, the safety and effectiveness findings in this PMS were consistent with findings from previous clinical studies. Sorafenib was well tolerated and clinically useful for Japanese patients.
  
  
  BACKGROUND
  NCT01411436.
authors.affiliation: Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan. skaneko@m-kanazawa.jp.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuzaki
authors.affiliation: Department of Medical Oncology, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Furuse
authors.affiliation: Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Minami
authors.affiliation: Pharmacovigilance, Medical Affairs, Bayer Yakuhin, Ltd., Osaka, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okayama
authors.affiliation: Clinical Statistics, Product Development, Bayer Yakuhin, Ltd., Osaka, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sunaya
authors.affiliation: Medical Affairs Oncology and Hematology, Bayer Yakuhin, Ltd., Osaka, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Pharmacovigilance, Medical Affairs, Bayer Yakuhin, Ltd., Osaka, Japan.
authors.forename: Lyo
authors.initials: L
authors.lastname: Inuyama
authors.affiliation: Shimonoseki Kosei Hospital, Yamaguchi, Japan.
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Okita
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D002648:Child; D003967:Diarrhea / Q000139:chemically induced; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D060831:Hand-Foot Syndrome / Q000209:etiology; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007564:Japan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D062072:Patient Acuity; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D011358:Product Surveillance, Postmarketing; D011446:Prospective Studies; D012737:Sex Factors; D000077157:Sorafenib; D015996:Survival Rate; D028761:Withholding Treatment; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: Hepatocellular carcinoma; Japanese; Molecular targeted therapy; Postmarketing surveillance; Sorafenib