title: Pilot study of gefitinib and fulvestrant in the treatment of post-menopausal women with advanced non-small cell lung cancer.
abstract: BACKGROUND
  Estrogen receptor beta (ERbeta) has been detected in non-small cell lung cancer (NSCLC) cell lines and tumor specimens. The ER down-regulator, fulvestrant, blocked estradiol-stimulation of tumor growth and gene transcription in NSCLC preclinical models and showed additive effects with the epidermal growth factor receptor (EGFR) inhibitor gefitinib. The safety and tolerability of combination therapy with the EGFR inhibitor, gefitinib, and fulvestrant was explored.
  
  
  METHODS
  Post-menopausal women with advanced NSCLC received gefitinib 250 mg po daily and fulvestrant 250 mg IM monthly.
  
  
  RESULTS
  Twenty-two patients were enrolled. Eight patients had adenocarcinoma, six NSCLC-NOS, four squamous cell, and four BAC. Seven patients were never-smokers. Eight patients received > or =2 lines of prior chemotherapy, six received one prior chemotherapy, and eight were treatment-naïve. One patient experienced grade 4 dyspnea possibly related to treatment; all other grade 3/4 toxicities were unrelated to treatment. Twenty patients were evaluable for response: three partial responses (PRs) were confirmed (response rate of 15%, 95% CI: 5-36%). The median progression-free survival (PFS), overall survival (OS), and estimated 1-year OS were 12 weeks (3-112 weeks), 38.5 weeks (7-135 weeks), and 41% (95% CI: 20-62%), respectively. Survival outcomes did not differ by prior lines of therapy. A subset analysis revealed that OS in the eight patients whose tumors exhibited at least 60% ERbeta nuclear IHC staining measured 65.5 weeks, while that of the five patients with ERbeta staining of less than 60% was 21 weeks. One patient with bronchioalveolar carcinoma (BAC) and a PR had an EGFR L858R mutation in exon 21. There was no correlation between ERbeta IHC expression and histology or smoking history.
  
  
  CONCLUSIONS
  Combination therapy with gefitinib and fulvestrant in this population was well tolerated and demonstrated disease activity.
authors.affiliation: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States. amt@medicine.wisc.edu
authors.forename: Anne M
authors.initials: AM
authors.lastname: Traynor
authors.forename: Joan H
authors.initials: JH
authors.lastname: Schiller
authors.forename: Laura P
authors.initials: LP
authors.lastname: Stabile
authors.forename: Jill M
authors.initials: JM
authors.lastname: Kolesar
authors.forename: Jens C
authors.initials: JC
authors.lastname: Eickhoff
authors.forename: Sanja
authors.initials: S
authors.lastname: Dacic
authors.forename: Tien
authors.initials: T
authors.lastname: Hoang
authors.forename: Sarita
authors.initials: S
authors.lastname: Dubey
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Marcotte
authors.forename: Jill M
authors.initials: JM
authors.lastname: Siegfried
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000556:secondary; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D000077267:Fulvestrant; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010865:Pilot Projects; D017698:Postmenopause; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage; D012449:Safety; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D011799:Quinazolines; D000077267:Fulvestrant; D004958:Estradiol; D000077156:Gefitinib