title: Relationship between epidermal growth factor receptor gene mutations and the severity of adverse events by gefitinib in patients with advanced non-small cell lung cancer.
abstract: OBJECTIVE
  Recent reports have demonstrated that mutation of epidermal growth factor receptor (EGFR) gene is predictive factor for tumor responsiveness to gefitinib suggesting the importance of EGFR status for the treatment of the patients with non-small cell lung cancer (NSCLC). However, the relationship between EGFR mutation and adverse events of gefitinib is still unknown. The aim of this study was to evaluate its correlation.
  
  
  METHODS
  Twenty-six tumor samples from Japanese NSCLC patients who received gefitinib in Okayama University Hospital between November 2000 and October 2004 were examined exons 18-21 of EGFR using direct sequence method. We retrospectively reviewed the clinical records and compared EGFR mutation status with adverse events during gefitinib treatment.
  
  
  RESULTS
  Of all 26 patients, EGFR mutation (exon 19 in-frame deletion, 6; exon 21 L858R, 5), were detected in 11 patients (42.3%). The principal adverse event was skin rash (89%), diarrhea (39%), and liver injury (39%). Grade 3 or more adverse events were not common. EGFR mutation status was correlated with neither its frequency nor severity of adverse events during gefitinib treatment including skin rash, diarrhea, liver injury, and interstitial lung disease. As expected, objective response rate of those with EGFR mutations was significantly higher than those without EGFR mutations (78% versus 21%, P<0.001).
  
  
  CONCLUSIONS
  Our study did not demonstrate the presence of close relationships between EGFR mutation status and adverse events during gefitinib treatment.
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Toyooka
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Tokumo
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hotta
authors.forename: Motoi
authors.initials: M
authors.lastname: Aoe
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabata
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Date
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury; D003967:Diarrhea / Q000139:chemically induced; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D011799:Quinazolines / Q000009:adverse effects*; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib