title: Efficacy and safety of erlotinib monotherapy for Japanese patients with advanced non-small cell lung cancer: a phase II study.
abstract: BACKGROUND
  The aim of this study was to evaluate the efficacy and safety of Erlotinib in Japanese patients with previously treated non-small cell lung cancer (NSCLC). Available tumor biopsy samples were analyzed to examine relationships between biomarkers and clinical outcome.
  
  
  METHODS
  This open-label phase II trial enrolled stage III/IV NSCLC patients who had progressive disease after at least one prior platinum-based chemotherapy regimen. Erlotinib was administered at a dose of 150 mg/d orally until disease progression or intolerable toxicity. Analysis of epidermal growth factor receptor gene mutations in exon 18-21 by direct sequencing was performed in tumor tissue specimens obtained at the first diagnosis.
  
  
  RESULTS
  Sixty-two patients were enrolled and 60 patients were evaluable for efficacy. Objective response rate and disease control rate were 28.3% and 50.0%; median time to progression and overall survival were 77 days and 14.7 months, respectively. In logistic regression analysis, only smoking history was proved to be a statistically significant predictive factor for response (odds ratio: 0.06, p < 0.001). Only 7 patients had samples available for mutation analysis. Three patients who had deletion mutations on exon 19 (del E746-A750 or del S752-I759) exhibited objective response. Common toxicities were rash (98%), dry skin (81%), and diarrhea (74%). Discontinuation due to adverse events occurred in 11 patients (18%). Four patients (6%) experienced interstitial lung disease-like events, one of whom died.
  
  
  CONCLUSIONS
  Erlotinib is efficacious in Japanese patients with previously treated NSCLC. The toxicity profile was similar to that in Western patients, except for a somewhat higher incidence of skin disorders and interstitial lung disease. Further studies are needed to determine the relationship between epidermal growth factor receptor mutations and outcomes with Erlotinib in Japanese patients.
authors.affiliation: National Cancer Center Hospital East, Kashiwa, Chiba, Japan. kkubota@east.ncc.go.jp
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kubota
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nishiwaki
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Kaoru
authors.initials: K
authors.lastname: Matsui
authors.forename: Koshiro
authors.initials: K
authors.lastname: Watanabe
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hida
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kawahara
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katakami
authors.forename: Koji
authors.initials: K
authors.lastname: Takeda
authors.forename: Akira
authors.initials: A
authors.lastname: Yokoyama
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Noda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuoka
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Saijo
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D000328:Adult; D000368:Aged; D044466:Asian People; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000556:secondary; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors