title: Early skin toxicity as a predictive factor for tumor control in hepatocellular carcinoma patients treated with sorafenib.
abstract: BACKGROUND
  Sorafenib is an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases and has led to a longer median overall survival (OS) time and time to progression (TTP) in patients with advanced hepatocellular carcinoma (HCC). This study was conducted to assess the link between the antitumor efficacy of sorafenib and its early cutaneous side effects in advanced HCC patients.
  
  
  METHODS
  All patients received 800 mg daily of sorafenib until progression or unacceptable toxicities. We retrospectively analyzed the incidence of rash and hand-foot skin reactions (HFSR) during the first month of treatment, comparing tumor control (partial response plus stable disease) and TTP.
  
  
  RESULTS
  Sixty-five HCC patients treated with sorafenib were included in this analysis: 47 (73.3%) received sorafenib after failure of some local treatment, whereas 18 (27.7%) received it as first-line treatment. Twenty-nine patients developed at least grade 1 skin toxicity (rash, 13; HFSR, 16). In patients who developed skin toxicity, the tumor control rate was 48.3%, versus 19.4% in patients without cutaneous side effects. The median TTP was 8.1 months in the group of patients with skin toxicity versus 4.0 months in those without skin toxicity. This difference was also statistically significant on multivariate analysis. A borderline statistically significant difference was also observed in terms of OS in patients with early skin toxicity.
  
  
  CONCLUSIONS
  Skin toxicity should be closely monitored in HCC patients treated with sorafenib in relation to its potential role as a surrogate marker of efficacy.
authors.affiliation: Department of Surgical and Oncological Sciences, Section of Medical Oncology; Università di Palermo, Palermo, Italy, Via del Vespro 127, 90127 Palermo, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: Raffaele
authors.initials: R
authors.lastname: Addeo
authors.forename: Francesco
authors.initials: F
authors.lastname: Giuliani
authors.forename: Liliana
authors.initials: L
authors.lastname: Montella
authors.forename: Sergio
authors.initials: S
authors.lastname: Rizzo
authors.forename: Olga
authors.initials: O
authors.lastname: Venditti
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Frezza
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Colucci
authors.forename: Salvatore
authors.initials: S
authors.lastname: Del Prete
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D018450:Disease Progression; D003875:Drug Eruptions / Q000209:etiology*; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D000077157:Sorafenib; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib