title: Pazopanib combined with radiation: in vivo model of interaction.
abstract: OBJECTIVE
  Assess interaction of pazopanib, an oral antivascular endothelial growth factor inhibitor, with radiation in tumor xenograft models.
  
  
  METHODS
  Flank xenografts in female athymic nude mice of human lung cancer cell line, A549, and head and neck cancer cell line, UM-SCC-6, were allowed to grow to ∼5×5 mm. Groups were then treated with pazopanib and/or escalating doses of radiation and tumor measurements over time compared with untreated tumor-bearing controls. Pazopanib (100 mg/kg) began 7 days before radiation and continued for 28 days. Daily radiation was 0.5, 1, 2, or 3 Gy ×5 days.
  
  
  RESULTS
  Tumors in the A549 control group reached >4× the original size by day 36 postradiation. All treatment groups had less robust tumor growth (p<0.05) and the group receiving pazopanib+3 Gy radiation/day had tumor regression to less than baseline. In the UM-SCC-6-tumor-bearing animals, tumors in all treatment groups had less robust growth than untreated controls after day 23 post-treatment.
  
  
  CONCLUSIONS
  The combination of pazopanib and radiation resulted in a trend of superior tumor growth inhibition compared with either agent alone. All treatment groups had impaired tumor progression compared with untreated controls.
authors.affiliation: 1 Department of Radiation Oncology, University of Alabama at Birmingham , Birmingham, Alabama.
authors.forename: Ruby F
authors.initials: RF
authors.lastname: Meredith
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Raisch
authors.forename: James A
authors.initials: JA
authors.lastname: Bonner
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Buchsbaum
authors.forename: Willliam E
authors.initials: WE
authors.lastname: Grizzle
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Li
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Spencer
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005260:Female; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D007191:Indazoles; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000532:radiotherapy*; D051379:Mice; D008819:Mice, Nude; D011743:Pyrimidines / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib
keywords: pazopanib; radiation; xenograft tumor model