title: A phase II study evaluating axitinib in patients with unresectable, recurrent or metastatic head and neck cancer.
abstract: BACKGROUND
  Axitinib is an oral, potent, small molecule tyrosine kinase inhibitor with selective inhibition of VEGFR 1,2, 3, as well as inhibition of potential downstream effectors of the EGFR pathway. Given the upregulation of EGFR and VEGFR in head and neck squamous cell carcinoma, treatment with axitinib holds promise as a rational targeted therapy.
  
  
  METHODS
  Patients with unresectable, recurrent or metastatic head and neck squamous cell carcinoma were included in this open label, single arm, phase II trial. Primary endpoint was 6 month progression free survival. All patients received single agent axitinib with planned dose escalation based on tolerability. A planned interim efficacy analysis was performed after enrollment of 30 patients.
  
  
  RESULTS
  Forty-two patients were registered, 30 were evaluable. While treatment was well-tolerated with no severe bleeding events, only 19 patients were able to achieve full planned dose. The best overall response rate was 6.7% (two partial responses) with a disease control rate of 76.7%. Median progression free survival was 3.7 months (95% Confidence Interval (CI): 3.5-5.7) and overall survival was 10.9 months (95% CI: 6.4-17.8). Exploratory analysis demonstrated that patients with a smaller sum of diameter of target lesions experienced improved response rates, and better progression-free and overall survival.
  
  
  CONCLUSIONS
  Treatment with single agent axitinib should be considered due to acceptable toxicity profile and favorable median overall survival compared to standard therapies.
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA. pswiecic@med.umich.edu.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Swiecicki
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhao
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Belile
authors.affiliation: University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Assuntina G
authors.initials: AG
authors.lastname: Sacco
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Chepeha
authors.affiliation: Department of Oncology, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Dobrosotskaya
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Spector
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Shuman
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Malloy
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Moyer
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: McKean
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: McLean
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Wolf
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Avraham
authors.initials: A
authors.lastname: Eisbruch
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Prince
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Bradford
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Carey
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Francis P
authors.initials: FP
authors.lastname: Worden
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077784:Axitinib; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007093:Imidazoles / Q000627:therapeutic use*; D007191:Indazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015996:Survival Rate / Q000639:trends
chemical_list: D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D000077784:Axitinib
keywords: Axitinib; Head and neck cancer; Squamous cell carcinoma; Tyrosine kinase inhibitor; Vascular endothelial growth factor receptor