AZD2171, a Pan-VEGF Receptor Tyrosine Kinase Inhibitor, Normalizes Tumor Vasculature and Alleviates Edema in Glioblastoma Patients

Tracy T. Batchelor, A. Gregory Sorensen, Emmanuelle di Tomaso, Wei Ting Zhang, Dan G G. Duda, Kenneth S. Cohen, Kevin R. Kozak, Daniel P. Cahill, Poe Jou Chen, Mingwang Zhu, Marek Ancukiewicz, Maciej M. Mrugala, Scott Plotkin, Jan Drappatz, David N. Louis, Percy Ivy, David T T. Scadden, Thomas Benner, Jay S. Loeffler, Patrick Y. WenRakesh K. Jain

Research output: Contribution to journalArticle

1403 Scopus citations

Abstract

Using MRI techniques, we show here that normalization of tumor vessels in recurrent glioblastoma patients by daily administration of AZD2171-an oral tyrosine kinase inhibitor of VEGF receptors-has rapid onset, is prolonged but reversible, and has the significant clinical benefit of alleviating edema. Reversal of normalization began by 28 days, though some features persisted for as long as four months. Basic FGF, SDF1α, and viable circulating endothelial cells (CECs) increased when tumors escaped treatment, and circulating progenitor cells (CPCs) increased when tumors progressed after drug interruption. Our study provides insight into different mechanisms of action of this class of drugs in recurrent glioblastoma patients and suggests that the timing of combination therapy may be critical for optimizing activity against this tumor.

Original languageEnglish (US)
Pages (from-to)83-95
Number of pages13
JournalCancer cell
Volume11
Issue number1
DOIs
StatePublished - Jan 2007

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Batchelor, T. T., Sorensen, A. G., di Tomaso, E., Zhang, W. T., Duda, DG. G., Cohen, K. S., Kozak, K. R., Cahill, D. P., Chen, P. J., Zhu, M., Ancukiewicz, M., Mrugala, M. M., Plotkin, S., Drappatz, J., Louis, D. N., Ivy, P., Scadden, DT. T., Benner, T., Loeffler, J. S., ... Jain, R. K. (2007). AZD2171, a Pan-VEGF Receptor Tyrosine Kinase Inhibitor, Normalizes Tumor Vasculature and Alleviates Edema in Glioblastoma Patients. Cancer cell, 11(1), 83-95. https://doi.org/10.1016/j.ccr.2006.11.021