title: Gefitinib, cisplatin, and concurrent radiotherapy for locally advanced head and neck cancer: EGFR FISH, protein expression, and mutational status are not predictive biomarkers.
abstract: BACKGROUND
  Gefitinib was demonstrated to be synergistic with cisplatin and radiotherapy (RT) in in vitro studies. Biomarkers predictive of response to gefitinib in squamous cell head and neck cancer is still lacking.
  
  
  METHODS
  Thirty-one patients with locally advanced and easily accessible primary tumor sites for biopsies were recruited. Gefitinib was started 3 weeks before the start of cisplatin/concurrent radiotherapy (CTRT) and continued during the CTRT phase and thereafter for 4 months as consolidation phase. Two baselines and a repeat tumor sample were taken after 2 weeks of gefitinib alone to study its impact on tumor gene expression. Epidermal growth factor receptor (EGFR) protein expression, FISH and mutational status, and matrix metallopeptidase 11 (MMP11) protein expression were correlated with response and survival outcome.
  
  
  RESULTS
  The overall response rate to gefitinib alone was 9.7%. The survival outcome is as follows: median disease free 1.3 years, median survival time 2.4 years, 3-year disease free 42.9%, and 3-year overall survival 48.4%. EGFR FISH, protein expression, and mutational status did not predict for response nor survival outcome of patients. Although MMP11 overexpression did not predict for response, it predicted significantly for a poorer survival outcome.
  
  
  CONCLUSIONS
  Gefitinib can be combined safely with cisplatin/RT. More studies are needed to uncover predictive biomarkers of benefit to gefitinib.
authors.affiliation: Department of Medical Oncology, National Cancer Centre, Singapore. dmoteh@nccs.com.sg
authors.forename: E-H
authors.initials: EH
authors.lastname: Tan
authors.forename: C
authors.initials: C
authors.lastname: Goh
authors.forename: W T
authors.initials: WT
authors.lastname: Lim
authors.forename: K C
authors.initials: KC
authors.lastname: Soo
authors.forename: M L
authors.initials: ML
authors.lastname: Khoo
authors.forename: T
authors.initials: T
authors.lastname: Tan
authors.forename: D S W
authors.initials: DS
authors.lastname: Tan
authors.forename: M K
authors.initials: MK
authors.lastname: Ang
authors.forename: Q S
authors.initials: QS
authors.lastname: Ng
authors.forename: P H
authors.initials: PH
authors.lastname: Tan
authors.forename: A
authors.initials: A
authors.lastname: Lim
authors.forename: J
authors.initials: J
authors.lastname: Hwang
authors.forename: Y H F
authors.initials: YH
authors.lastname: Teng
authors.forename: T H
authors.initials: TH
authors.lastname: Lim
authors.forename: S H
authors.initials: SH
authors.lastname: Tan
authors.forename: N
authors.initials: N
authors.lastname: Baskaran
authors.forename: K M
authors.initials: KM
authors.lastname: Hui
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D000077156:Gefitinib; D015870:Gene Expression; D020869:Gene Expression Profiling; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D053507:Matrix Metalloproteinase 11 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011799:Quinazolines / Q000008:administration & dosage; D012307:Risk Factors; D012907:Smoking; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D011799:Quinazolines; D066246:ErbB Receptors; C511771:MMP11 protein, human; D053507:Matrix Metalloproteinase 11; D002945:Cisplatin; D000077156:Gefitinib