title: Phase II trial of gefitinib 250 mg daily in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.
abstract: OBJECTIVE
  An objective response rate of 11% was reported in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) treated with 500 mg daily gefitinib although the recommended dose in lung cancer is 250 mg. This study evaluated the efficacy and toxicity of 250 mg daily gefitinib in patients with recurrent and/or metastatic SCCHN.
  
  
  METHODS
  Phase II trial with objective response rate as the primary end point. Measurements of quality of life and levels of serum vascular endothelial growth factor and transforming growth factor-alpha were assessed before and during therapy.
  
  
  RESULTS
  In 70 patients, 1 (1.4%) partial response was observed. Median progression-free survival and overall survival were 1.8 and 5.5 months, respectively. Quality of life scores improved transiently during the first weeks of therapy before returning to baseline. Median vascular endothelial growth factor and transforming growth factor-alpha levels were above the normal range but were not predictive of outcome. Four patients experienced grade 3 drug-related adverse events. Rash of any grade was observed in 64% of subjects. Correlation between disease control (partial response + stable disease), progression-free survival, and overall survival and grade of cutaneous toxicity was observed (P = 0.001, 0.001, and 0.008 respectively).
  
  
  CONCLUSIONS
  Gefitinib monotherapy at 250 mg in recurrent and/or metastatic SCCHN seems to have less activity than was previously observed for 500 mg daily. A dose-response relationship may exist for this agent in SCCHN and grade of cutaneous toxicity attributable to gefitinib is a clinical predictor of better outcome.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago, IL 60637, USA. ecohen@medicine.bsd.uchicago.edu
authors.forename: Ezra E W
authors.initials: EE
authors.lastname: Cohen
authors.forename: Madeleine A
authors.initials: MA
authors.lastname: Kane
authors.forename: Marcy A
authors.initials: MA
authors.lastname: List
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Brockstein
authors.forename: Bhoomi
authors.initials: B
authors.lastname: Mehrotra
authors.forename: Dezheng
authors.initials: D
authors.lastname: Huo
authors.forename: Ann M
authors.initials: AM
authors.lastname: Mauer
authors.forename: Carolyn
authors.initials: C
authors.lastname: Pierce
authors.forename: Allison
authors.initials: A
authors.lastname: Dekker
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D000077156:Gefitinib; D006258:Head and Neck Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy*; D011788:Quality of Life; D011799:Quinazolines / Q000627:therapeutic use*; D016879:Salvage Therapy; D015996:Survival Rate; D016211:Transforming Growth Factor alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D016211:Transforming Growth Factor alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077156:Gefitinib