title: Sorafenib for the treatment of advanced hepatocellular carcinoma with extrahepatic metastasis: a prospective multicenter cohort study.
abstract: Sorafenib, an oral multikinase inhibitor, is approved for advanced hepatocellular carcinoma (HCC) treatment. However, its therapeutic effect in advanced HCC patients with extrahepatic metastasis remains uncertain. This study aimed to prospectively assess the efficacy, safety, and survival risk factors and evaluate the prognostic impact of sorafenib treatment in advanced HCC patients with or without extrahepatic metastasis. Between May 2009 and March 2014, 312 consecutive advanced HCC patients who received sorafenib were enrolled in this study. We evaluated their characteristics and compared the clinical outcomes of those with and without extrahepatic metastasis. Of the enrolled patients, 245 (81%) received sorafenib treatment for more than 1 month, with a median duration of 3.6 months. Eighteen patients demonstrated partial response to sorafenib therapy, 127 had stable disease, and 134 had progressive disease at the first radiologic assessment. The median survival time (MST) and progression-free survival (PFS) were 10.3 and 3.6 months, respectively. Multivariate analysis identified gender, Child-Pugh class, baseline serum des-gamma-carboxy prothrombin level, and treatment duration as independent risk factors for survival. Extrahepatic metastasis was detected in 178 patients. However, the MST, PFS, and therapeutic effect were comparable between patients with and without extrahepatic metastasis. The independent risk factors for decreased overall survival in patients with extrahepatic metastasis were similar to those affecting all patients. Our results indicated that sorafenib could be administered for hepatic reserve and as long-term treatment for advanced HCC patients regardless of their extrahepatic metastasis status.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Nakano
authors.affiliation: Yokokura Hospital, Miyama, Fukuoka, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Kuromatsu
authors.affiliation: Yame General Hospital, Yame, Fukuoka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagamatsu
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Tajiri
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Satani
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Niizeki
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Aino
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Okamura
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Iwamoto
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Shimose
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Tomotake
authors.initials: T
authors.lastname: Shirono
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Koga
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Torimura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010349:Patient Compliance; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib
keywords: Extrahepatic metastasis; hepatic reserve; hepatocellular carcinoma; long-term treatment; sorafenib