title: Phase I study of vandetanib with radiation therapy with or without cisplatin in locally advanced head and neck squamous cell carcinoma.
abstract: BACKGROUND
  Vandetanib, added to cisplatin and radiation therapy (RT) overcomes chemoradiation therapy (CRT) and epidermal growth factor receptor (EGFR) inhibitor resistance in head and neck squamous cell carcinoma (HNSCC) lines and models.
  
  
  METHODS
  Patients with previously untreated HNSCC received vandetanib daily for 14 days (starting dose 100 mg) and then vandetanib + RT (2.2 Gy/day, 5 days/week) for 6 weeks (regimen 1) or vandetanib + RT (2 Gy/day, 5 days/week) + cisplatin (30 mg/m(2) weekly) for 7 weeks (regimen 2). The primary objective was the maximum tolerated dose (MTD) of vandetanib with RT +/- cisplatin.
  
  
  RESULTS
  Of 33 treated patients, 30 completed therapy (regimen 1, n = 12; regimen 2, n = 18). MTD in regimen 2 was 100 mg (3 dose limiting toxicities [DLTs] at 200 mg), whereas regimen 1 was stopped because of poor recruitment (1 DLT at 200 mg). Most common grade ≥3 adverse events (AEs) were dysphagia (30%), stomatitis (33%), and mucosal inflammation (27%). Five patients discontinued vandetanib because of AEs.
  
  
  CONCLUSIONS
  Vandetanib with CRT was feasible.
authors.affiliation: Department of Thoracic Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Vasiliki A
authors.initials: VA
authors.lastname: Papadimitrakopoulou
authors.affiliation: Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Frank
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Ezra W
authors.initials: EW
authors.lastname: Cohen
authors.affiliation: University of Colorado Cancer Center, Aurora, Colorado.
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
authors.affiliation: Department of Head and Neck Surgery, University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Myers
authors.affiliation: Department of Thoracic Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, Texas.
authors.forename: John V
authors.initials: JV
authors.lastname: Heymach
authors.affiliation: Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Heather
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Thoracic Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Hai T
authors.initials: HT
authors.lastname: Tran
authors.affiliation: Department of Radiation Oncology, University of Toledo, Toledo, Ohio.
authors.forename: Changhu R
authors.initials: CR
authors.lastname: Chen
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Antonio
authors.initials: A
authors.lastname: Jimeno
authors.affiliation: Department of Radiation Oncology, Southwestern Medical Center, Dallas, Texas.
authors.forename: Lucien
authors.initials: L
authors.lastname: Nedzi
authors.affiliation: AstraZeneca Pharmaceuticals, Wilmington, Delaware.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Vasselli
authors.affiliation: AstraZeneca Pharmaceuticals, Wilmington, Delaware.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Lowe
authors.affiliation: Department of Oncology, University of Colorado, Aurora, Colorado.
authors.forename: David
authors.initials: D
authors.lastname: Raben
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000008:administration & dosage; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D010880:Piperidines; D011799:Quinazolines; D011505:Protein-Tyrosine Kinases; D002945:Cisplatin; C452423:vandetanib
keywords: cisplatin; head and neck squamous cell cancer; radiation therapy; vandetanib