title: Indicators of sorafenib efficacy in patients with advanced hepatocellular carcinoma.
abstract: OBJECTIVE
  To determine significant indicators for the efficacy of sorafenib in patients with advanced hepatocellular carcinoma (HCC).
  
  
  METHODS
  A total of 46 patients with Barcelona Clinic Liver Cancer stage C who received sorafenib for more than 30 d at the Iizuka Hospital from June 2009 to December 2012 were enrolled in this study. Multivariate and univariate analyses were performed to evaluate the associations of hepatic function according to Child-Pugh grade, location and size of the largest tumor and adverse events of sorafenib treatment, such as hand-foot syndrome (HFS), hypertension, diarrhea, and alopecia, with the efficacy of treatment, as measured by overall survival (OS) and time to progression (TTP).
  
  
  RESULTS
  Patients included 39 men and 7 women whose ages ranged from 48 to 85 years (70.6 ± 9.6 years). HCC was classified according to etiology as follows: hepatitis C virus (n = 26), hepatitis B virus (n = 9), and other (n = 11). Liver function in patients was categorized as Child-Pugh grade A (n = 30) or B (n = 16). Tumors were categorized by size [< 5 cm (n = 33) or >5 cm (n = 13)] and the location of the largest tumor was used to categorize patients with intrahepatic (n = 28) or extrahepatic (n = 18) HCC. HFS, hypertension, diarrhea, and alopecia were present in 22 (47.8%), 19 (41.3%), 15 (32.6%) and 7 patients (15.2%), respectively. The median OS of all patients was 373 d and the median TTP was 112 d. The etiology of HCC did not correlate with the median OS and TPP. The median OS of patients with tumors < 5 cm was significantly longer than those with larger tumors (496 vs 245 d; HR = 0.19, 95%CI: 0.07-0.48; P < 0.01). According to the results of a multivariate analysis, the size of the largest tumor affected OS (HR = 0.22, 95%CI: 0.08-0.59; P < 0.01). The median TTP was significantly longer in patients with extrahepatic compared to intrahepatic major HCC (224 vs 98 d; HR = 0.32; 95%CI: 0.14-0.67; P < 0.01). The median TTP of patients with HFS was significantly longer than those without it (195 d vs 83 d; HR = 0.41, 95%CI: 0.20-0.82; P < 0.05), and the median TTP was significantly longer in patients with hypertension (195 d vs 84 d; HR = 0.43, 95%CI: 0.21-0.84; P < 0.05). According to the results of the multivariate analysis, extrahepatic major HCC (HR = 0.36, P < 0.01) and HFS (HR = 0.44, P < 0.05) prolonged TTP.
  
  
  CONCLUSIONS
  Extrahepatic major HCC and HFS are associated with prolonged TTP and are useful indicators for judging the efficacy of sorafenib treatment.
authors.affiliation: Masayoshi Yada, Akihide Masumoto, Kenta Motomura, Hirotaka Tajiri, Yusuke Morita, Hideo Suzuki, Takeshi Senju, Toshimasa Koyanagi, Department of Hepatology, Iizuka Hospital, Iizuka, Fukuoka 820-8505, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yada
authors.affiliation: Masayoshi Yada, Akihide Masumoto, Kenta Motomura, Hirotaka Tajiri, Yusuke Morita, Hideo Suzuki, Takeshi Senju, Toshimasa Koyanagi, Department of Hepatology, Iizuka Hospital, Iizuka, Fukuoka 820-8505, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Masumoto
authors.affiliation: Masayoshi Yada, Akihide Masumoto, Kenta Motomura, Hirotaka Tajiri, Yusuke Morita, Hideo Suzuki, Takeshi Senju, Toshimasa Koyanagi, Department of Hepatology, Iizuka Hospital, Iizuka, Fukuoka 820-8505, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Motomura
authors.affiliation: Masayoshi Yada, Akihide Masumoto, Kenta Motomura, Hirotaka Tajiri, Yusuke Morita, Hideo Suzuki, Takeshi Senju, Toshimasa Koyanagi, Department of Hepatology, Iizuka Hospital, Iizuka, Fukuoka 820-8505, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Tajiri
authors.affiliation: Masayoshi Yada, Akihide Masumoto, Kenta Motomura, Hirotaka Tajiri, Yusuke Morita, Hideo Suzuki, Takeshi Senju, Toshimasa Koyanagi, Department of Hepatology, Iizuka Hospital, Iizuka, Fukuoka 820-8505, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Morita
authors.affiliation: Masayoshi Yada, Akihide Masumoto, Kenta Motomura, Hirotaka Tajiri, Yusuke Morita, Hideo Suzuki, Takeshi Senju, Toshimasa Koyanagi, Department of Hepatology, Iizuka Hospital, Iizuka, Fukuoka 820-8505, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Masayoshi Yada, Akihide Masumoto, Kenta Motomura, Hirotaka Tajiri, Yusuke Morita, Hideo Suzuki, Takeshi Senju, Toshimasa Koyanagi, Department of Hepatology, Iizuka Hospital, Iizuka, Fukuoka 820-8505, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Senju
authors.affiliation: Masayoshi Yada, Akihide Masumoto, Kenta Motomura, Hirotaka Tajiri, Yusuke Morita, Hideo Suzuki, Takeshi Senju, Toshimasa Koyanagi, Department of Hepatology, Iizuka Hospital, Iizuka, Fukuoka 820-8505, Japan.
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Koyanagi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D060831:Hand-Foot Syndrome / Q000209:etiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D012307:Risk Factors; D000077157:Sorafenib; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib
keywords: Hand-foot syndrome; Hepatocellular carcinoma; Indicator of efficacy; Sorafenib; Time to progression