title: Comparative dosing and efficacy of sorafenib in hepatocellular cancer patients with varying liver dysfunction.
abstract: BACKGROUND
  Sorafenib is the only FDA-approved systemic therapy for advanced hepatocellular carcinoma (HCC). In clinical practice, dose reductions are often required, although there are limited efficacy data related to dose modifications. Given the prevalence of HCC in South Texas, we assessed the efficacy and safety of sorafenib therapy in relation to dose and Child Pugh (CP) score.
  
  
  METHODS
  A retrospective analysis was done of advanced HCC patients, starting sorafenib at 400 mg twice daily, or at physician discretion at 400 mg daily, with the goal of titrating to twice daily. Overall survival (OS) and progression-free survival (PFS) were assessed.
  
  
  RESULTS
  Among 107 patients, median OS (mOS) was 10.2 months; median PFS (mPFS) was 5.2 months. mOS for sorafenib 400 mg/day was 6.6 vs. 800 mg/day was 12.8 months [hazard ratio (HR), 0.59; P=0.04]; mPFS was 3.5 vs. 5.9 months, respectively (HR, 0.66; P=0.07). For Child Pugh A class (CP-A) patients, mOS was 15.8 months for 400 mg/day vs. 12.8 months for 800 mg/day (HR, 1.48; P=0.35); mPFS was 9.0 vs. 5.9 months, respectively (HR, 1.23; P=0.56). For Child Pugh B class (CP-B) patients, mOS was 5.0 months for 400 mg/day vs. 11.2 months for 800 mg/day (HR, 0.33; P=0.002); mPFS was 2.1 vs. 5.6 months, respectively (HR, 0.41; P=0.006). No differences in adverse events (AEs) were observed in CP-A vs. CP-B.
  
  
  CONCLUSIONS
  Patients with CP-A or CP-B advanced HCC should be offered sorafenib at 400 mg twice daily with optimal management of AEs in order to improve survival.
authors.affiliation: University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA.
authors.forename: Raed
authors.initials: R
authors.lastname: Al-Rajabi
authors.affiliation: University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA.
authors.forename: Sukeshi
authors.initials: S
authors.lastname: Patel
authors.affiliation: University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA.
authors.forename: Norma S
authors.initials: NS
authors.lastname: Ketchum
authors.affiliation: University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Jaime
authors.affiliation: University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA.
authors.forename: Ting-Wei
authors.initials: TW
authors.lastname: Lu
authors.affiliation: University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA.
authors.forename: Brad H
authors.initials: BH
authors.lastname: Pollock
authors.affiliation: University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA.
authors.forename: Devalingam
authors.initials: D
authors.lastname: Mahalingam
keywords: Child Pugh (CP) cirrhosis; Liver cancer; hepatobiliary; metastatic