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

  • Clinical Study – Patient Study
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Abstract

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.

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Acknowledgments

We would like to acknowledge the patients who consented to participate in this study, their families, the Wetenschappelijk Fonds Willy Gepts of the UZ Brussel for the financial support, and Pfizer Belgium for the provision of sunitinib study medication and a research grant. We would also like to thank the data manager Katrien Van den Bossche (UZ Brussel) for data collection and analysis, Ms Annariikka Roselli for excellent technical assistance, and Ludwig Van den Hove, PhD, Pfizer Belgium, for his support and critical review of the manuscript.

Conflict of interest

B. Neyns has received financial compensation for public speaking from Schering-Plough and Merck/Serono, research funding from Schering-Plough, Merck/Serono, and Pfizer.

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Authors and Affiliations

  1. Department of Medical Oncology, UZ Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium

    B. Neyns, J. Sadones, S. Lv & J. De Greve

  2. Department of Neurosurgery, UZ Brussel, Brussels, Belgium

    C. Chaskis & J. Duerinck

  3. Department of Radiology, UZ Brussel, Brussels, Belgium

    M. Dujardin

  4. Department of Nuclear Medicine, UZ Brussel, Brussels, Belgium

    H. Everaert

  5. Department of Pathology, University of Helsinki, Helsinki, Finland

    O. Tynninen & N. Nupponen

  6. Department of Neurology, UZ Brussel, Brussels, Belgium

    A. Michotte

  7. Department of Neuropathology, UZ Brussel, Brussels, Belgium

    A. Michotte

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Neyns, B., Sadones, J., Chaskis, C. et al. Phase II study of sunitinib malate in patients with recurrent high-grade glioma. J Neurooncol 103, 491–501 (2011). https://doi.org/10.1007/s11060-010-0402-7

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  • DOI: https://doi.org/10.1007/s11060-010-0402-7

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