title: Polymorphisms of the epidermal growth factor receptor (EGFR) and survival in patients with advanced cancer of the head and neck (HNSCC).
abstract: OBJECTIVE
  Associations between polymorphisms of the epidermal growth factor receptor (EGFR) and overall survival in patients with advanced carcinoma of the head and neck (HNSCC) receiving cetuximab based palliative treatment, were evaluated.
  
  
  METHODS
  HNSCC patients (n=48) received cetuximab +/- chemotherapy. Samples for DNA extraction and clinical data were collected prospectively. Genotyping of four EGF(R) polymorphisms was performed using PCR-based restriction fragment length polymorphism (RFLP).
  
  
  RESULTS
  The median overall survival was 10.6 months. The EGFR-R497K polymorphism was significantly associated with overall survival. The presence of at least one K-allele was associated with shorter overall survival. The median survival in these patients was 6.7 months compared to 13.3 months in the patients homozygous for the wild type allele EGFR-497R (p=0.009). Addition of chemotherapy to cetuximab, age and EGFR-R497K polymorphism were independent predictors of overall survival. Multivariate analysis revealed a hazard ratio (HR) for patients with at least one EGFR-497K allele of 3.03 when compared with EGFR-497R homozygous patients (p=0.045).
  
  
  CONCLUSIONS
  The EGFR-R497K polymorphism is a potential predictor for overall survival in HNSCC patients treated with cetuximab based therapy in the palliative setting.
authors.affiliation: Department of Internal Medicine I, Fetscherstr. 74, 01307 Dresden, Germany. jan.stoehlmacher@uniklinikum-dresden.de
authors.forename: Jan
authors.initials: J
authors.lastname: Stoehlmacher-Williams
authors.forename: Luise
authors.initials: L
authors.lastname: Obermann
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Eray
authors.initials: E
authors.lastname: Goekkurt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000068818:Cetuximab; D002945:Cisplatin / Q000008:administration & dosage; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016190:Carboplatin; D066246:ErbB Receptors; D000068818:Cetuximab; D002945:Cisplatin