title: A phase I trial of erlotinib and concurrent chemoradiotherapy for stage III and IV (M0) squamous cell carcinoma of the head and neck.
abstract: OBJECTIVE
  Erlotinib, an orally active selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, has synergistic activity with radiation and with cisplatin. The EGFR is overexpressed in the majority of head and neck cancers. The primary objective of this phase I study was to determine the maximum-tolerated dose (MTD) of erlotinib in combination with low-dose daily cisplatin and radiotherapy. We also sought evidence of biologic activity of erlotinib alone using serial 18-FDG positron emission tomography (PET) imaging.
  
  
  METHODS
  Oral erlotinib was taken daily starting with a 14-day run-in and continued until radiation therapy (RT) was completed. Low-dose daily cisplatin, 6 mg/m(2) i.v. was given concurrently with standard fractionation RT to a total dose of 66 to 70 Gy. Dose escalation followed a modified Fibonacci dose escalation design.
  
  
  RESULTS
  Twenty-two patients were enrolled and 18 patients received therapy on protocol. MTD of the combination of erlotinib, cisplatin, and RT was not reached. The recommended phase II dose of erlotinib is 150 mg per day in combination with cisplatin and RT, the highest dose of erlotinib evaluated in this study. 18F-FDG PET showed evidence for metabolic response to single-agent erlotinib. Per PERCIST criteria, the overall metabolic response rate at day 14 was 38.8% (95% CI: 17.3-64.3). On completion of concurrent chemoradiotherapy, overall response rate derived from tumor measurements based on imaging studies was 83% for all dose levels combined.
  
  
  CONCLUSIONS
  Erlotinib in combination with low-dose daily cisplatin and RT is well tolerated and shows evidence of clinical efficacy. The combination should be evaluated further.
authors.affiliation: Vanderbilt University School of Medicine, Nashville, TN, USA. jill.gilbert@vanderbilt.edu
authors.forename: Jill
authors.initials: J
authors.lastname: Gilbert
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Rudek
authors.forename: Michaela J
authors.initials: MJ
authors.lastname: Higgins
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Sara
authors.initials: S
authors.lastname: Bienvenu
authors.forename: Nancy
authors.initials: N
authors.lastname: Tsottles
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Chaudhry
authors.forename: Richard
authors.initials: R
authors.lastname: Wahl
authors.forename: Arlene
authors.initials: A
authors.lastname: Forastiere
authors.forename: Maura
authors.initials: M
authors.lastname: Gillison
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D019583:Dose Fractionation, Radiation; D000069347:Erlotinib Hydrochloride; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D002945:Cisplatin