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Updated: Jun 8, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Phase II study of sunitinib malate in patients with recurrent high-grade glioma
B Neyns1, J Sadones, C Chaskis
1Department of Medical Oncology, UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. Bart.Neyns@uzbrussel.be
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.
Insights
Sunitinib malate did not show significant efficacy in treating recurrent high-grade gliomas (HGG). The anti-angiogenic therapy demonstrated limited impact on tumor progression and survival rates in patients with advanced HGG.
Area of Science:
- Oncology
- Neuro-oncology
- Molecular Biology
Background:
- Receptor tyrosine kinase signaling drives neo-angiogenesis in high-grade gliomas (HGG).
- KIT, PDGFR-α, and VEGFR2 genes are frequently amplified and expressed in HGG, representing therapeutic targets.
- Sunitinib malate is a small-molecule kinase inhibitor targeting these genes.
Purpose of the Study:
- To evaluate the anti-angiogenic effects and clinical activity of sunitinib malate in patients with progressive HGG.
- To assess the impact of sunitinib malate on tumor perfusion using MRI and DSC measurements.
Main Methods:
- Twenty-one patients with progressive HGG received daily sunitinib malate (37.5 mg).
- MRI and DSC-enhanced perfusion measurements (CBV, CBF) were conducted pre- and during therapy.
- Adverse events and clinical outcomes (progression, survival) were monitored.
Main Results:
- No objective responses were observed; all patients progressed within eight weeks.
- A decrease in CBV and CBF was noted in 29% of evaluable patients.
- Frequent adverse events included skin toxicity, neutropenia, and thrombocytopenia.
Conclusions:
- Single-agent sunitinib malate at 37.5 mg/day showed insufficient activity for recurrent HGG.
- Further investigation of this monotherapy regimen is not warranted.
- The study did not establish a correlation between gene copy numbers/protein expression and sunitinib's effects.
