Angiogenesis inhibitor DC101 delays growth of intracerebral glioblastoma but induces morbidity when combined with irradiation

Cancer Lett. 2009 Nov 18;285(1):39-45. doi: 10.1016/j.canlet.2009.04.038. Epub 2009 May 26.

Abstract

The combination of irradiation with angiogenic inhibition is increasingly being investigated for treatment of glioblastoma multiforme (GBM). We investigated whether vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitor DC101 affects morbidity and tumor growth in irradiated and non-irradiated intracerebral GBM-bearing mice, controlled with sham treatments. End-points were toxicity, morbidity and histology. Irradiation either or not combined, reduced tumor size strongly, whereas DC101 mono-treatment reduced tumor size by 64%. Irradiation delayed morbidity from 5.8 weeks in sham-treated mice to 10.3 weeks. Morbidity after combined treatment occurred after 5.9 weeks. Treatment with angiogenesis inhibitor DC101 delays tumor growth but it induces morbidity, by itself or combined with irradiation.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / toxicity
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / toxicity
  • Brachytherapy* / adverse effects
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / radiotherapy
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Chemotherapy, Adjuvant
  • Cranial Irradiation* / adverse effects
  • Female
  • Glioblastoma / blood supply
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Glioblastoma / radiotherapy
  • Humans
  • Mice
  • Mice, Nude
  • Necrosis
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / prevention & control*
  • Radiotherapy, Adjuvant
  • Time Factors
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • DC101 monoclonal antibody
  • Vascular Endothelial Growth Factor Receptor-2