Phase II study of sunitinib malate in patients with recurrent high-grade glioma.
J Neurooncol
; 103(3): 491-501, 2011 Jul.
Article
en En
| MEDLINE
| ID: mdl-20872043
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirroles
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Neoplasias del Sistema Nervioso Central
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Glioma
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Indoles
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Antineoplásicos
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Neurooncol
Año:
2011
Tipo del documento:
Article
País de afiliación:
Bélgica
Pais de publicación:
Estados Unidos