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

Author(s): Neyns B, Sadones J, Chaskis C, Dujardin M, Everaert H, Lv S, Duerinck J, Tynninen O, Nupponen N, Michotte A, De Greve J

Affiliation(s): Department of Medical Oncology, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. Bart.Neyns@uzbrussel.be

Publication date & source: 2011-07, J Neurooncol., 103(3):491-501. Epub 2010 Sep 25.

Publication type: Clinical Trial, Phase II; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

Receptor tyrosine kinase signaling causes profound neo-angiogenesis in high-grade gliomas (HGG). The KIT, PDGFR-alpha, 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-alpha, 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.

Page last updated: 2011-12-09

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