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Molecular targeted therapies and chemotherapy in malignant gliomas

Brandsma, Dietaa; van den Bent, Martin Jb

doi: 10.1097/CCO.0b013e3282f0313b
Brain and nervous system: Edited by Jerzy Hildebrand

Purpose of review To review current developments in the field of chemotherapy and targeted treatment of high-grade glioma.

Recent findings Two independent large phase III trials on adjuvant procarbazine, lomustine and vincristine chemotherapy in anaplastic oligodendroglial tumors have shown this improves progression-free survival, but not overall survival, regardless of 1p/19q status. If given sequentially, the timing of procarbazine, lomustine and vincristine chemotherapy has no clear effect on the survival of anaplastic oligodendroglioma. Virtually none of the many new targeted agents directed against pathways that are upregulated in high-grade gliomas has shown significant clinical activity as single agent in phase II studies. The exception are trials with the vascular endothelial growth factor signaling system inhibiting agents bevacizumab and AZD2171 (cediranib) that showed high response rates (which might be due to vessel normalization similar to the effects of steroid treatment) and promising 6-month progression-free survival rates in glioblastoma multiforme.

Summary Further research to define the role of vascular endothelial growth factor inhibition in the management is indicated. For the many other targeted agents, a critical review of the pathological role of their targets in glioblastoma multiforme is required, especially if combination regimens are investigated. The role of combined chemo-irradiation for non-glioblastoma multiforme high-grade glioma remains to be identified.

aDepartment of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands

bNeuro-Oncology Unit, Daniël den Hoed Cancer Center/Erasmus University Hospital, Rotterdam, The Netherlands

Correspondence to M.J. van den Bent, Neuro-Oncology Unit, Daniel den Hoed Cancer Center/Erasmus University Hospital, PO Box 5201, 3008AE Rotterdam, The Netherlands Tel: +31 10 4391415; fax: +31 10 4391031; e-mail:

© 2007 Lippincott Williams & Wilkins, Inc.