title: Gefitinib frequently induces liver damage in patients with lung adenocarcinoma previously treated by chemotherapy.
abstract: BACKGROUND
  Gefitinib is known as one of the agents for treating patients with both advanced lung cancer and an epidermal growth-factor receptor mutation. In the epidermal growth-factor receptor-mutant advanced non-small-cell lung cancer population, gefitinib therapy has been associated with increased response rate, longer progression-free survival, and better quality of life compared to other anticancer drugs. However, gefitinib has to be discontinued for patients in whom adverse events occur, even if it is still effective. Here, we retrospectively assessed the clinical course of patients receiving gefitinib therapy, with a particular focus on liver damage.
  
  
  METHODS
  Of 24 Asian patients treated with 250 mg gefitinib daily at Kanagawa National Hospital, Japan, between January 2008 and June 2012, grade 3 liver damage (Common Terminology Criteria for Adverse Events, version 4.0) occurred in nine and were eligible for our assessment. The regimen was subsequently changed to alternate-day administration. The relationships between liver damage and each clinical factor were retrospectively examined using Fisher's exact test.
  
  
  RESULTS
  Of the nine patients with liver damage, seven had previous exposure to another anticancer drug. There was a significant relationship between the incidence of liver damage and previous chemotherapy (P= 0.009). The objective response rates of patients treated with daily gefitinib 250 mg and alternate-day gefitinib following liver damage were 66.7% and 46.7%, respectively; these were not significantly different (P= 0.597).
  
  
  CONCLUSIONS
  Gefitinib for advanced adenocarcinoma patients who have previously undergone chemotherapy should be used cautiously and liver function monitored closely, because it frequently induces significant liver damage. The alternate-day administration of gefitinib may be a suitable option for patients in whom daily gefitinib therapy induces liver damage.
authors.affiliation: Department of Pulmonary and Thoracic Surgery.
authors.forename: Yasoo
authors.initials: Y
authors.lastname: Sugiura
authors.affiliation: Department of Pulmonary and Thoracic Surgery.
authors.forename: Etsuo
authors.initials: E
authors.lastname: Nemoto
authors.affiliation: Department of Respiratory Medicine, Kanagawa National Hospital, Hadano, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kawai
authors.affiliation: Department of Respiratory Medicine, Kanagawa National Hospital, Hadano, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohkubo
authors.affiliation: Department of Respiratory Medicine, Kanagawa National Hospital, Hadano, Japan.
authors.forename: Hisae
authors.initials: H
authors.lastname: Fusegawa
authors.affiliation: Department of Pulmonary and Thoracic Surgery.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Kaseda
keywords: adjuvant chemotherapy; alternate-day administration; gefitinib; liver damage; previous chemotherapy