Increased survival of glioblastoma patients who respond to antiangiogenic therapy with elevated blood perfusion

Cancer Res. 2012 Jan 15;72(2):402-7. doi: 10.1158/0008-5472.CAN-11-2464. Epub 2011 Nov 29.

Abstract

The abnormal vasculature of the tumor microenvironment supports progression and resistance to treatment. Judicious application of antiangiogenic therapy may normalize the structure and function of the tumor vasculature, promoting improved blood perfusion. However, direct clinical evidence is lacking for improvements in blood perfusion after antiangiogenic therapy. In this study, we used MRI to assess tumor blood perfusion in 30 recurrent glioblastoma patients who were undergoing treatment with cediranib, a pan-VEGF receptor tyrosine kinase inhibitor. Tumor blood perfusion increased durably for more than 1 month in 7 of 30 patients, in whom it was associated with longer survival. Together, our findings offer direct clinical evidence in support of the hypothesis that vascular normalization can increase tumor perfusion and help improve patient survival.

Trial registration: ClinicalTrials.gov NCT00035656.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Brain Neoplasms / blood supply*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Disease Progression
  • Disease-Free Survival
  • Glioblastoma / blood supply*
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Neoplasm Recurrence, Local / blood supply*
  • Neoplasm Recurrence, Local / drug therapy*
  • Quinazolines / therapeutic use*
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
  • Survival Rate

Substances

  • Angiogenesis Inhibitors
  • Quinazolines
  • Receptors, Vascular Endothelial Growth Factor
  • cediranib

Associated data

  • ClinicalTrials.gov/NCT00035656

Grants and funding