title: A phase II trial of gefitinib monotherapy in chemotherapy-naïve patients of 75 years or older with advanced non-small cell lung cancer.
abstract: BACKGROUND
  Gefitinib has shown modest activity in patients with recurrent non-small cell lung cancer (NSCLC) after platinum-based chemotherapy. However, the activity of gefitinib as first-line chemotherapy remains unclear, especially unknown in elderly patients. A multicenter phase II trial was conducted to evaluate the efficacy and tolerability of gefitinib for elderly patients with chemotherapy-naïve NSCLC.
  
  
  METHODS
  Elderly chemotherapy-naïve patients with advanced NSCLC, ECOG PS of 0-2, and adequate organ functions received 250 mg/day of gefitinib. The primary objective of this study was to determine the objective response rate (RR). Secondary endpoints were tolerability, disease-related symptom using lung cancer subscale (LCS) in FACT-L, progression free survival (PFS) and overall survival (OS). We investigated mutation status of the epidermal growth factor receptor (EGFR) gene in cases with available tumor samples.
  
  
  RESULTS
  Fifty patients were enrolled, of whom 49 were eligible. Median age (range) was 80 (75-90) years. Thirty-two patients were female (65%) and 40 patients had adenocarcinoma (82%). The objective RR was 25% (CI 95%, 13-39). Median survival time was 10 months (CI 95%, 7-20) and 1-year survival rate was 50%. The most frequent adverse events were skin disorders (76%). Fifteen patients (30%) experienced toxicities >/=grade 3. There were four patients with possible interstitial lung disease including two treatment-related deaths. Symptom improvement rate using LCS was 49% at 4 weeks of gefitinib therapy. Tumor samples from 17 patients were analyzed for EGFR mutation status. EGFR mutations were detected in tumor tissues from 7 patients, of which 5 had partial responses (71%).
  
  
  CONCLUSIONS
  Gefitinib monotherapy is effective and relatively well tolerated in chemotherapy-naïve elderly patients with advanced NSCLC. Gefitinib has potential as a first-line therapeutic option in elderly patients with advanced NSCLC.
authors.affiliation: Department of Respiratory Medicine, Iizuka Hospital, Fukuoka, Japan. nebi1@aih-net.com
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ebi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Semba
authors.forename: Sho J I
authors.initials: SJ
authors.lastname: Tokunaga
authors.forename: Koichi
authors.initials: K
authors.lastname: Takayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wataya
authors.forename: Takashige
authors.initials: T
authors.lastname: Kuraki
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Shin J I
authors.initials: SJ
authors.lastname: Akamine
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000556:secondary; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006306:Health Surveys; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D009367:Neoplasm Staging; D011379:Prognosis; D011788:Quality of Life; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib