title: The gefitinib dose reduction on survival outcomes in epidermal growth factor receptor mutant non-small cell lung cancer.
abstract: OBJECTIVE
  Gefitinib is safe for the treatment of non-small cell lung cancer (NSCLC), but some patients experience toxicities and require dose reduction. The purpose of this study was to evaluate the effect of gefitinib dose reduction on survival.
  
  
  METHODS
  We retrospectively analyzed 263 patients with NSCLC harboring sensitive epidermal growth factor receptor (EGFR) mutation. All patients had recurred or metastatic disease and received gefitinib 250 mg daily as palliative chemotherapy.
  
  
  RESULTS
  Of the 263 patients, 23 had gefitinib dose reduction due to toxicities (1 due to mucositis, 5 due to skin rash, 11 due to hepatotoxicity and 6 for both skin and hepatotoxicity). In the dose reduction group, the mean dose intensity was 0.84 (range 0.48-0.98). Patients with dose reduction showed significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to those receiving the standard dose (median PFS: 14.0 vs. 10.6 months, P = 0.042, median OS: 54.5 vs. 29.6, P = 0.020). In multivariate analysis, the effect of dose reduction was not significantly associated with prolonged PFS [hazard ratio (HR) 0.619, 95 % confidence interval (CI) 0.357-1.073, P = 0.085], or OS (HR 0.625, 95 % CI 0.287-1.362, P = 0.237). However, patients receiving low-dose gefitinib tended to have superior survival outcomes compared to those receiving standard-dose gefitinib.
  
  
  CONCLUSIONS
  The patients experiencing gefitinib dose reduction or short-term treatment interruption due to toxicities did not show inferior survival, compared to those receiving full dose of gefitinib in NSCLC patients with EGFR mutation.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Sim
authors.forename: Bhumsuk
authors.initials: B
authors.lastname: Keam
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011799:Quinazolines / Q000008:administration & dosage*; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib