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

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