title: Predictors of survival in patients with established cirrhosis and hepatocellular carcinoma treated with sorafenib.
abstract: OBJECTIVE
  To investigate in greater detail the efficacy and safety of sorafenib for the treatment of hepatocellular carcinoma (HCC) in patients with established cirrhosis.
  
  
  METHODS
  From October 2009 to July 2012 patients with an established diagnosis of cirrhosis and HCC treated with sorafenib were consecutively enrolled. According to the Barcelona Clinic Liver Cancer (BCLC) classification, patients were in the advanced stage (BCLC-C) or in the intermediate stage (BCLC-B) but unfit or unresponsive to other therapeutic strategies. Treatment was evaluated performing a 4-phase computed tomography or magnetic resonance imaging scan every 2-3 mo, and analyzed according to the modified Response Evaluation Criteria in Solid Tumors. Sorafenib was administered at 800 mg/d, until radiological progression or occurrence of unacceptable adverse events (AEs). Univariate and multivariate analyses identified predictors of 16-wk clinical benefit and overall survival.
  
  
  RESULTS
  Forty-four patients were enrolled, 15 had intermediate HCC and 14 a Child-Pugh score of B7. AEs caused treatment interruption in 19 patients (43%), and median treatment duration was shorter in this subset (5 wk vs 19 wk, P < 0.001) and in the BCLC-C subgroup (13 wk vs 40 wk, P = 0.015). No significant differences in the reason for treatment interruption or in treatment duration were found comparing patients in Child-Pugh class A vs B or in patients older or younger than 70 years. After 16 wk of treatment, 18 patients (41%) had stable disease or partial response. Patients with viral infection or BCLC-C were at higher risk of disease progression. ECOG, extrahepatic spread, macrovascular invasion, alpha-fetoprotein or alkaline phosphatase levels at admission were independent predictors of overall survival.
  
  
  CONCLUSIONS
  In patients with cirrhosis and HCC treated with sorafenib, AEs are a common cause of early treatment withdrawal. Vascular invasion and extrahepatic spread condition early response to treatment and survival. Baseline biochemical parameters may be helpful to identify patients at higher risk of shorter overall survival.
authors.affiliation: Andrea L Inghilesi, Donatella Gallori, Umberto Arena, Bernardo Fani, Giacomo Laffi, Fabio Marra, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, I-50134 Florence, Italy.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Inghilesi
authors.affiliation: Andrea L Inghilesi, Donatella Gallori, Umberto Arena, Bernardo Fani, Giacomo Laffi, Fabio Marra, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, I-50134 Florence, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Gallori
authors.affiliation: Andrea L Inghilesi, Donatella Gallori, Umberto Arena, Bernardo Fani, Giacomo Laffi, Fabio Marra, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, I-50134 Florence, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Antonuzzo
authors.affiliation: Andrea L Inghilesi, Donatella Gallori, Umberto Arena, Bernardo Fani, Giacomo Laffi, Fabio Marra, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, I-50134 Florence, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Forte
authors.affiliation: Andrea L Inghilesi, Donatella Gallori, Umberto Arena, Bernardo Fani, Giacomo Laffi, Fabio Marra, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, I-50134 Florence, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Tomcikova
authors.affiliation: Andrea L Inghilesi, Donatella Gallori, Umberto Arena, Bernardo Fani, Giacomo Laffi, Fabio Marra, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, I-50134 Florence, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Arena
authors.affiliation: Andrea L Inghilesi, Donatella Gallori, Umberto Arena, Bernardo Fani, Giacomo Laffi, Fabio Marra, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, I-50134 Florence, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Colagrande
authors.affiliation: Andrea L Inghilesi, Donatella Gallori, Umberto Arena, Bernardo Fani, Giacomo Laffi, Fabio Marra, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, I-50134 Florence, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pradella
authors.affiliation: Andrea L Inghilesi, Donatella Gallori, Umberto Arena, Bernardo Fani, Giacomo Laffi, Fabio Marra, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, I-50134 Florence, Italy.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Fani
authors.affiliation: Andrea L Inghilesi, Donatella Gallori, Umberto Arena, Bernardo Fani, Giacomo Laffi, Fabio Marra, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, I-50134 Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Gianni
authors.affiliation: Andrea L Inghilesi, Donatella Gallori, Umberto Arena, Bernardo Fani, Giacomo Laffi, Fabio Marra, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, I-50134 Florence, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Boni
authors.affiliation: Andrea L Inghilesi, Donatella Gallori, Umberto Arena, Bernardo Fani, Giacomo Laffi, Fabio Marra, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, I-50134 Florence, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Laffi
authors.affiliation: Andrea L Inghilesi, Donatella Gallori, Umberto Arena, Bernardo Fani, Giacomo Laffi, Fabio Marra, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, I-50134 Florence, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Costanzo
authors.affiliation: Andrea L Inghilesi, Donatella Gallori, Umberto Arena, Bernardo Fani, Giacomo Laffi, Fabio Marra, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, I-50134 Florence, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Marra
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; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000150:complications* / Q000401:mortality; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000473:pathology; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; 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*; D012307:Risk Factors; D000077157:Sorafenib; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib
keywords: Adverse events; Barcelona Clinic Liver Cancer; Cirrhosis; Hepatocellular carcinoma; Sorafenib