title: Sorafenib in the treatment of hepatocellular carcinoma: a multi-centre real-world study.
abstract: OBJECTIVE
  Sorafenib is an oral multikinase inhibitor that improves survival in advanced hepatocellular carcinoma (HCC). In the absence of alternative therapies, sorafenib is often continued despite advancing liver disease or tumour progression. Real world studies are important to better characterise outcomes in these populations. Our aim was to review patterns of sorafenib use across eight Australian tertiary hospitals, defining variables associated with clinical outcomes.
  
  
  METHODS
  Retrospective cohort study of medical records of 320 patients treated with sorafenib for HCC. Baseline clinical parameters, dosage, adverse effects, and survival from initiation of treatment were collected. Time to radiological progression and 3-month alpha-fetoprotein (AFP) levels were available for a subset of patients.
  
  
  RESULTS
  Adverse effects occurred in 79% of patients, requiring dose reduction in 31% of patients. Multivariate analysis identified an increased rate of mortality with Child-Pugh C (HR 5.52, p = 0.012), ECOG performance status 2-3 (HR 2.84, p = 0.001), and extrahepatic metastases (HR 1.54, p = 0.04), and decreased rate of mortality with an AFP reduction of at least 20% at 3 months (HR 0.38, p = 0.001). An increased rate of radiological progression was associated with ECOG performance status 2-3 (HR 2.34, p = 0.041), whilst a decreased rate of radiological progression was associated with development of on-treatment diarrhoea (HR 0.55, p = 0.015).
  
  
  CONCLUSIONS
  Survival in patients with Child-Pugh C liver function or advanced functional impairment treated with sorafenib is poor and thus routine use of this agent in these patients does not appear justified, particularly given the high rate of adverse effects. AFP concentration on therapy may help identify favourable response to treatment.
authors.affiliation: a Department of Gastroenterology , Monash Health , Victoria , Australia ;
authors.forename: Adam
authors.initials: A
authors.lastname: Doyle
authors.affiliation: a Department of Gastroenterology , Monash Health , Victoria , Australia ;
authors.forename: Philip
authors.initials: P
authors.lastname: Marsh
authors.affiliation: b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , New South Wales , Australia ;
authors.forename: Raghubinder
authors.initials: R
authors.lastname: Gill
authors.affiliation: b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , New South Wales , Australia ;
authors.forename: Marcia
authors.initials: M
authors.lastname: Rodov
authors.affiliation: b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , New South Wales , Australia ;
authors.forename: Waled
authors.initials: W
authors.lastname: Mohsen
authors.affiliation: c Department of Gastroenterology and Hepatology , Royal Melbourne Hospital , Victoria , Australia ;
authors.forename: Poornima
authors.initials: P
authors.lastname: Varma
authors.affiliation: d Department of Gastroenterology , St Vincent's Hospital , Victoria , Australia ;
authors.forename: Thai
authors.initials: T
authors.lastname: Hong
authors.affiliation: b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , New South Wales , Australia ;
authors.forename: Simone I
authors.initials: SI
authors.lastname: Strasser
authors.affiliation: d Department of Gastroenterology , St Vincent's Hospital , Victoria , Australia ;
authors.forename: Sally
authors.initials: S
authors.lastname: Bell
authors.affiliation: d Department of Gastroenterology , St Vincent's Hospital , Victoria , Australia ;
authors.forename: Marno
authors.initials: M
authors.lastname: Ryan
authors.affiliation: c Department of Gastroenterology and Hepatology , Royal Melbourne Hospital , Victoria , Australia ;|e Department of Gastroenterology , Box Hill Hospital, Eastern Health , Victoria , Australia ;
authors.forename: Amanda
authors.initials: A
authors.lastname: Nicoll
authors.affiliation: e Department of Gastroenterology , Box Hill Hospital, Eastern Health , Victoria , Australia ;
authors.forename: John
authors.initials: J
authors.lastname: Lubel
authors.affiliation: f Department of Gastroenterology , Austin Health , Victoria , Australia ;
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Gow
authors.affiliation: g Department of Surgery , Austin Health , Melbourne , Victoria , Australia ;
authors.forename: Michael Anthony
authors.initials: MA
authors.lastname: Fink
authors.affiliation: h Department of Gastroenterology , Alfred Hospital , Victoria , Australia ;
authors.forename: Stuart
authors.initials: S
authors.lastname: Roberts
authors.affiliation: h Department of Gastroenterology , Alfred Hospital , Victoria , Australia ;
authors.forename: William
authors.initials: W
authors.lastname: Kemp
authors.affiliation: i Department of Gastroenterology , Western Hospital , Victoria , Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Kronborg
authors.affiliation: i Department of Gastroenterology , Western Hospital , Victoria , Australia.
authors.forename: Niranjan
authors.initials: N
authors.lastname: Arachchi
authors.affiliation: a Department of Gastroenterology , Monash Health , Victoria , Australia ;
authors.forename: Virginia
authors.initials: V
authors.lastname: Knight
authors.affiliation: a Department of Gastroenterology , Monash Health , Victoria , Australia ;
authors.forename: Anouk
authors.initials: A
authors.lastname: Dev
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D000077157:Sorafenib; D016896:Treatment Outcome; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D000509:alpha-Fetoproteins; D009536:Niacinamide; D000077157:Sorafenib
keywords: Adverse effects; multivariate analysis; progression; survival