title: Phase II study of gefitinib adaptive dose escalation to skin toxicity in recurrent or metastatic squamous cell carcinoma of the head and neck.
abstract: BACKGROUND
  Gefitinib has activity in patients with advanced squamous cell carcinoma of the head and neck (SCCHN) and skin toxicity has been postulated to be a predictor of response and improved outcome.
  
  
  METHODS
  This open-label, multi-institution, phase II study evaluated the activity of gefitinib at individually escalated doses up to 750 mg to achieve the skin toxicity grade ≥2.
  
  
  RESULTS
  Forty four patients were enrolled. Only twenty-three (52%) experienced skin rash grade ≥2. Of 44 patients, partial responses were noted in 3 (7%), stable disease in 8 (18%) and progressive disease in 33 patients. Median progression-free survival was 1.9 months (95% CI 1.6-2.2) and median overall survival was 5.1 months (95% CI 2.4-7.8). Grade of skin rash was not associated with response rate (p=0.169) nor tumor control rate (p=0.284); however, higher gefitinib trough levels were associated with disease control. Of the 11 tissue samples analyzed for EGFR gene copy by FISH, 7 were EGFR FISH positive, but this was not associated with improved tumor control or survival.
  
  
  CONCLUSIONS
  Gefitinib has clinical activity as monotherapy in SCCHN. Dose escalation of gefitinib is feasible and may increase skin toxicity, but our data do not support increased activity.
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Perez
authors.forename: Hunho
authors.initials: H
authors.lastname: Song
authors.forename: Luis E
authors.initials: LE
authors.lastname: Raez
authors.forename: Mark
authors.initials: M
authors.lastname: Agulnik
authors.forename: Tatyana A
authors.initials: TA
authors.lastname: Grushko
authors.forename: Allison
authors.initials: A
authors.lastname: Dekker
authors.forename: Kerstin
authors.initials: K
authors.lastname: Stenson
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Blair
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
authors.forename: Tanguy Y
authors.initials: TY
authors.lastname: Seiwert
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Ezra E W
authors.initials: EE
authors.lastname: Cohen
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D000077156:Gefitinib; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011799:Quinazolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib