Phase II study of sunitinib malate in patients with recurrent high-grade glioma

J Neurooncol. 2011 Jul;103(3):491-501. doi: 10.1007/s11060-010-0402-7. Epub 2010 Sep 25.


Receptor tyrosine kinase signaling causes profound neo-angiogenesis in high-grade gliomas (HGG). The KIT, PDGFR-α, and VEGFR2 genes are frequently amplified and expressed in HGG and are molecular targets for therapeutic inhibition by the small-molecule kinase inhibitor sunitinib malate. Twenty-one patients with progressive HGG after prior radiotherapy and chemotherapy received a daily dose of 37.5 mg sunitinib until progression or unacceptable toxicity. Magnetic resonance imaging (MRI) and dynamic susceptibility contrast (DSC)-enhanced perfusion measurements were performed before and during therapy. Cerebral blood volume (CBV) and cerebral blood flow (CBF) lesion-to-normal-white matter ratios were measured to evaluate the antiangiogenic effects of sunitinib. The most frequent grade ≥3 adverse events were skin toxicity, neutropenia, thrombocytopenia, and lymphocytopenia. None of the patients achieved an objective response, whereas a decrease in CBV and CBF within the lesion compared with the normal brain was documented in four out of 14 (29%) patients evaluable for DSC-enhanced perfusion measurements. All patients experienced progression of their disease before or after eight weeks of therapy. Median time-to-progression and overall survival were 1.6 (95%CI 0.8-2.5) and 3.8 (95% CI 2.2-5.3) months, respectively. No correlation could be established between VEGFR2, PDGFR-α, and KIT gene copy numbers or protein expression and the effects of sunitinib. Single-agent sunitinib at 37.5 mg/day had insufficient activity to warrant further investigation of this monotherapy regimen in recurrent HGG.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Central Nervous System Neoplasms / diagnosis
  • Central Nervous System Neoplasms / drug therapy*
  • Central Nervous System Neoplasms / pathology
  • Cerebrovascular Circulation
  • Disease Progression
  • Female
  • Glioma / diagnosis
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Indoles / therapeutic use*
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Proto-Oncogene Proteins c-kit / metabolism
  • Pyrroles / therapeutic use*
  • Pyrrolidinones
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Recurrence
  • Regional Blood Flow / drug effects
  • Sunitinib
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism


  • 5-((3-fluoromethoxy)phenyl)-3-(1-phenylethylamino)-1-(4-trifluoromethylphenyl)pyrrolidin-2-one
  • Antineoplastic Agents
  • Indoles
  • Pyrroles
  • Pyrrolidinones
  • Proto-Oncogene Proteins c-kit
  • Receptors, Platelet-Derived Growth Factor
  • Vascular Endothelial Growth Factor Receptor-2
  • Sunitinib