title: Skin toxicities and survival in advanced hepatocellular carcinoma patients treated with sorafenib.
abstract: OBJECTIVE
  Sorafenib is the first small molecule with significant clinical activity for advanced hepatocellular carcinoma (HCC). However, intolerable adverse events are sometimes observed. On the other hand, it has been reported that some toxicities of molecular targeted drugs, such as skin toxicities and arterial hypertension, are correlated with good clinical outcomes in other cancers.
  
  
  METHODS
  We identified the correlations between adverse events and prognosis for sorafenib therapy in all patients with HCC treated at the institutions of the Saga Liver Cancer Study Group. The toxicities were assessed using the Common Terminology Criteria for Adverse Events version 4.0.
  
  
  RESULTS
  Ninety-four patients received sorafenib until August 2010. The overall incidence of treatment-related adverse events was 98% of patients. Skin toxicities, including palmar-plantar erythrodysesthesia syndrome, rash, pruritus and alopecia, were the most common adverse events and were observed in 58 patients (62%). Hypertension was observed in 23 patients (24%). The median survival time was 12.5 months among the total patients. The patients with skin toxicities showed significantly longer survival than the patients without these toxicities (hazard ratio, 0.449; 95% confidence interval, 0.256-0.786; P = 0.005). Hypertension had no correlation with survival. Skin toxicities were also significant prognostic factors in a multivariate analysis (hazard ratio, 0.522; 95% confidence interval, 0.274-0.997; P = 0.049), along with Child-Pugh class and α-fetoprotein level. The median development time for skin toxicities was 21 days.
  
  
  CONCLUSIONS
  Skin toxicities occur commonly at the early phase in patients treated with sorafenib, and could be a promising surrogate marker for the treatment outcome.
authors.affiliation: Department of Internal Medicine, Hepatobiliary and Pancreatology Division, Saga Prefectural Hospital, Ureshino, Japan.
authors.forename: Taiga
authors.initials: T
authors.lastname: Otsuka
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Eguchi
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawazoe
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Yanagita
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ario
authors.forename: Kenji
authors.initials: K
authors.lastname: Kitahara
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kawasoe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Mizuta