title: Phase II trial of gefitinib in recurrent glioblastoma.
abstract: OBJECTIVE
  To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma.
  
  
  METHODS
  This was an open-label, single-center phase II trial. Fifty-seven patients with first recurrence of a glioblastoma who were previously treated with surgical resection, radiation, and usually chemotherapy underwent an open biopsy or resection at evaluation for confirmation of tumor recurrence. Each patient initially received 500 mg of gefitinib orally once daily; dose escalation to 750 mg then 1,000 mg, if a patient received enzyme-inducing antiepileptic drugs or dexamethasone, was allowed within each patient.
  
  
  RESULTS
  Although no objective tumor responses were seen among the 53 assessable patients, only 21% of patients (11 of 53 patients) had measurable disease at treatment initiation. Seventeen percent of patients (nine of 53 patients) underwent at least six 4-week cycles, and the 6-month event-free survival (EFS) was 13% (seven of 53 patients). The median EFS time was 8.1 weeks, and the median overall survival (OS) time from treatment initiation was 39.4 weeks. Adverse events were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent at higher doses. Withdrawal caused by drug-related adverse events occurred in 6% of patients (three of 53 patients). Although the presence of diarrhea positively predicted favorable OS from treatment initiation, epidermal growth factor receptor expression did not correlate with either EFS or OS.
  
  
  CONCLUSIONS
  Gefitinib is well tolerated and has activity in patients with recurrent glioblastoma. Further study of this agent at higher doses is warranted.
authors.affiliation: Duke University Medical Center, Box 2900, Durham, NC 27710, USA. rich0001@mc.duke.edu
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Rich
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.forename: Terry
authors.initials: T
authors.lastname: Peery
authors.forename: Jeannette M
authors.initials: JM
authors.lastname: Dowell
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Quinn
authors.forename: Kara L
authors.initials: KL
authors.lastname: Penne
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Wikstrand
authors.forename: Lauren B
authors.initials: LB
authors.lastname: Van Duyn
authors.forename: Janet E
authors.initials: JE
authors.lastname: Dancey
authors.forename: Roger E
authors.initials: RE
authors.lastname: McLendon
authors.forename: James C
authors.initials: JC
authors.lastname: Kao
authors.forename: Timothy T
authors.initials: TT
authors.lastname: Stenzel
authors.forename: B K
authors.initials: BK
authors.lastname: Ahmed Rasheed
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Tourt-Uhlig
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.forename: James J
authors.initials: JJ
authors.lastname: Vredenburgh
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
authors.forename: Allan H
authors.initials: AH
authors.lastname: Friedman
authors.forename: Darell D
authors.initials: DD
authors.lastname: Bigner
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors; D005260:Female; D000077156:Gefitinib; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D004791:Enzyme Inhibitors; D011799:Quinazolines; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib