Prognostic value and kinetics of circulating endothelial cells in patients with recurrent glioblastoma randomised to bevacizumab plus lomustine, bevacizumab single agent or lomustine single agent. A report from the Dutch Neuro-Oncology Group BELOB trial

Angiogenesis is crucial for glioblastoma growth, and anti-vascular endothelial growth factor agents are widely used in recurrent glioblastoma patients. The number of circulating endothelial cells (CECs) is a surrogate marker for endothelial damage. We assessed their kinetics and explored their progn...

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Bibliographic Details
Published in:British journal of cancer 2015-07, Vol.113 (2), p.226-231
Main Authors: Beije, N, Kraan, J, Taal, W, van der Holt, B, Oosterkamp, H M, Walenkamp, A M, Beerepoot, L, Hanse, M, van Linde, M E, Otten, A, Vernhout, R M, de Vos, F Y F, Gratama, J W, Sleijfer, S, van den Bent, M J
Format: Article
Language:English
Subjects:
Adult
Aged
Antibodies, Monoclonal, Humanized - administration & dosage
Antibodies, Monoclonal, Humanized - therapeutic use
Antigens, CD - analysis
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Bevacizumab
Brain Neoplasms - drug therapy
Brain Neoplasms - mortality
Brain Neoplasms - pathology
Cell Movement
Clinical Study
Endothelial Cells - cytology
Endothelial Cells - physiology
Female
Glioblastoma - drug therapy
Glioblastoma - mortality
Glioblastoma - pathology
GPI-Linked Proteins - analysis
Humans
Kinetics
Lomustine - administration & dosage
Lomustine - therapeutic use
Male
Middle Aged
Neoplasm Proteins - analysis
Neoplasm Recurrence, Local - drug therapy
Neoplasm Recurrence, Local - mortality
Neoplasm Recurrence, Local - pathology
Prognosis
Proportional Hazards Models
Prospective Studies
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Summary:Angiogenesis is crucial for glioblastoma growth, and anti-vascular endothelial growth factor agents are widely used in recurrent glioblastoma patients. The number of circulating endothelial cells (CECs) is a surrogate marker for endothelial damage. We assessed their kinetics and explored their prognostic value in patients with recurrent glioblastoma. In this side study of the BELOB trial, 141 patients with recurrent glioblastoma were randomised to receive single-agent bevacizumab or lomustine, or bevacizumab plus lomustine. Before treatment, after 4 weeks and after 6 weeks of treatment, CECs were enumerated. The number of CECs increased during treatment with bevacizumab plus lomustine, but not during treatment in the single-agent arms. In patients treated with lomustine single agent, higher absolute CEC numbers after 4 weeks (log₁₀CEC hazard ratio (HR) 0.41, 95% CI 0.18-0.91) and 6 weeks (log₁₀CEC HR 0.16, 95% CI 0.05-0.56) of treatment were associated with improved overall survival (OS). Absolute CEC numbers in patients receiving bevacizumab plus lomustine or bevacizumab single agent were not associated with OS. CEC numbers increased during treatment with bevacizumab plus lomustine but not during treatment with either agent alone, suggesting that this combination induced the greatest vascular damage. Although the absolute number of CECs was not associated with OS in patients treated with bevacizumab either alone or in combination, they could serve as a marker in glioblastoma patients receiving lomustine single agent.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2015.191