title: Epidermal growth factor receptor inhibitor gefitinib added to chemoradiotherapy in locally advanced head and neck cancer.
abstract: OBJECTIVE
  Assess efficacy and toxicity of gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, added to, and in maintenance after, concurrent chemoradiotherapy (CCRT) in locally advanced head and neck cancer (LA-HNC) and correlate outcomes with EGFR gene copy number alterations.
  
  
  METHODS
  Patients with stage III to IV LA-HNC received two cycles of carboplatin/paclitaxel induction chemotherapy (IC) followed by split-course CCRT with fluorouracil, hydroxyurea, twice daily radiotherapy (FHX), and gefitinib (250 mg daily) followed by continued gefitinib for 2 years total. The primary end point was complete response (CR) rate after CCRT. EGFR gene copy number was assessed by fluorescent in situ hybridization.
  
  
  RESULTS
  Sixty-nine patients (66 with stage IV disease, 37 with oropharynx primary tumors, and 67 with performance status 0 to 1) were enrolled with a median age of 55 years. Predominant grade 3 or 4 toxicities during IC and CCRT were neutropenia (n = 20) and in-field mucositis (n = 59) and dermatitis (n = 23), respectively. CR rate after CCRT was 90%. After median follow-up of 3.5 years, 4-year overall, progression-free, and disease-specific survival rates were 74%, 72%, and 89%, respectively. To date, one patient has developed a second primary tumor in the aerodigestive tract. In 31 patients with available tissue, high EGFR gene copy number was associated with worse overall survival (P = .02).
  
  
  CONCLUSIONS
  Gefitinib can be administered with FHX and as maintenance therapy for at least 2 years, demonstrating CR and survival rates that compare favorably with prior experience. High EGFR gene copy number may be associated with poor outcome in patients with LA-HNC treated with this regimen.
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL, USA. ecohen@medicine.bsd.uchicago.edu
authors.forename: Ezra E W
authors.initials: EE
authors.lastname: Cohen
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Haraf
authors.forename: Rangesh
authors.initials: R
authors.lastname: Kunnavakkam
authors.forename: Kerstin M
authors.initials: KM
authors.lastname: Stenson
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Blair
authors.forename: Bruce
authors.initials: B
authors.lastname: Brockstein
authors.forename: Eric P
authors.initials: EP
authors.lastname: Lester
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Salama
authors.forename: Allison
authors.initials: A
authors.lastname: Dekker
authors.forename: Rosalyn
authors.initials: R
authors.lastname: Williams
authors.forename: Mary Ellyn
authors.initials: ME
authors.lastname: Witt
authors.forename: Tatyana A
authors.initials: TA
authors.lastname: Grushko
authors.forename: James J
authors.initials: JJ
authors.lastname: Dignam
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lingen
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D000077156:Gefitinib; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage*
chemical_list: D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib