title: Clinical outcomes of patients with advanced hepatocellular carcinoma treated with sorafenib: a retrospective study of routine clinical practice in multi-institutions.
abstract: BACKGROUND
  Sorafenib is an orally administered multikinase inhibitor with antiangiogenic and antiproliferative properties. The results of large clinical trials demonstrate that sorafenib prolongs survival and the time to progression of patients with advanced hepatocellular carcinoma (HCC). The aim of the present study was to determine the outcomes of such patients who were routinely treated with sorafenib at multi-institutions in Korea, in contrast to formal clinical trials.
  
  
  METHODS
  Between August 2007 and March 2012, patients with advanced HCC in seven referral medical centers in Daejeon-Chungcheong Province of Korea were retrospectively enrolled to evaluate treatment response, survival, and tolerability following administration of sorafenib. The treatment response was assessed in accordance with the Response Evaluation Criteria in Solid Tumor 1.1 guidelines.
  
  
  RESULTS
  Among 116 patients, 66 (57%) had undergone treatment for HCC, and 77 (66%) were accompanied with Child-Pugh A cirrhosis. The median duration of sorafenib treatment was 67 days (range 14-452 days). Median overall survival and median time to progression were 141 days and 90 days, respectively. Complete response, partial response, and stable disease were achieved for 0%, 2%, and 29% of patients, respectively. Overall median survival, but not the median time to progression, was significantly shorter for patients with Child-Pugh B cirrhosis compared with those with Child-Pugh A cirrhosis (64 days vs 168 days, P = 0.004). Child-Pugh B cirrhosis (P = 0.024) and a high level of serum alpha-fetoprotein (P = 0.039) were independent risk factors for poor overall survival. Thirty-nine (34%) patients experienced grade 3/4 adverse events such as hand-foot skin reactions and diarrhea that required dose adjustment.
  
  
  CONCLUSIONS
  The clinical outcomes of sorafenib-treated patients with advanced HCC were comparable to those reported by formal clinical trial conducted in the Asia-Pacific region. Underlying hepatic dysfunction was the most important risk factor for shorter survival.
authors.affiliation: Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea. stevesh@sch.ac.kr.
authors.forename: Sae Hwan
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Dankook University College of Medicine, 201 Manghyang-ro, Dongnam-gu, Cheonan, 330-715, Republic of Korea. ihsong21@dankook.ac.kr.
authors.forename: Il Han
authors.initials: IH
authors.lastname: Song
authors.affiliation: Department of Internal Medicine, Dankook University College of Medicine, 201 Manghyang-ro, Dongnam-gu, Cheonan, 330-715, Republic of Korea. nonan3917@hanmail.net.
authors.forename: Ran
authors.initials: R
authors.lastname: Noh
authors.affiliation: Department of Internal Medicine, Dankook University College of Medicine, 201 Manghyang-ro, Dongnam-gu, Cheonan, 330-715, Republic of Korea. gkdis98@hanmail.net.
authors.forename: Ha Yan
authors.initials: HY
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Dankook University College of Medicine, 201 Manghyang-ro, Dongnam-gu, Cheonan, 330-715, Republic of Korea. sm1213@paran.com.
authors.forename: Suk Bae
authors.initials: SB
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Konkuk University School of Medicine, Chungju, Republic of Korea. syko406@hanmail.net.
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Ko
authors.affiliation: Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea. leeusgi@hanmail.net.
authors.forename: Eoum Seok
authors.initials: ES
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea. midoctor@cnuh.co.kr.
authors.forename: Seok Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea. gie001@cnuh.co.kr.
authors.forename: Byung Seok
authors.initials: BS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Eulji University College of Medicine, Daejeon, Republic of Korea. ankim@eulji.ac.kr.
authors.forename: An Na
authors.initials: AN
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Republic of Korea. hbchae@chungbuk.ac.kr.
authors.forename: Hee Bok
authors.initials: HB
authors.lastname: Chae
authors.affiliation: Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea. khskhs@sch.ac.kr.
authors.forename: Hong Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Republic of Korea. green740@naver.com.
authors.forename: Tae Hee
authors.initials: TH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Republic of Korea. kang45@kyuh.co.kr.
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Konkuk University School of Medicine, Chungju, Republic of Korea. jdongl@kku.ac.kr.
authors.forename: Jae Dong
authors.initials: JD
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea. leehy@cnu.ac.kr.
authors.forename: Heon Young
authors.initials: HY
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D012307:Risk Factors; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib