Molecular targeted therapies and chemotherapy in malignant gliomas.

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.