Chemoradiotherapy in malignant glioma: standard of care and future directions.
Details
Serval ID
serval:BIB_CC3FA7A8D6BF
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Chemoradiotherapy in malignant glioma: standard of care and future directions.
Journal
Journal of Clinical Oncology
ISSN
1527-7755[electronic]
Publication state
Published
Issued date
2007
Volume
25
Number
26
Pages
4127-4136
Language
english
Notes
Publication types: Journal Article ; Review
Abstract
Glioma has been considered resistant to chemotherapy and radiation. Recently, concomitant and adjuvant chemoradiotherapy with temozolomide has become the standard treatment for newly diagnosed glioblastoma. Conversely (neo-)adjuvant PCV (procarbazine, lomustine, vincristine) failed to improve survival in the more chemoresponsive tumor entities of anaplastic oligoastrocytoma and oligodendroglioma. Preclinical investigations suggest synergism or additivity of radiotherapy and temozolomide in glioma cell lines. Although the relative contribution of the concomitant and the adjuvant chemotherapy, respectively, cannot be assessed, the early introduction of chemotherapy and the simultaneous administration with radiotherapy appear to be key for the improvement of outcome. Epigenetic inactivation of the DNA repair enzyme methylguanine methyltransferase (MGMT) seems to be the strongest predictive marker for outcome in patients treated with alkylating agent chemotherapy. Patients whose tumors do not have MGMT promoter methylation are less likely to benefit from the addition of temozolomide chemotherapy and require alternative treatment strategies. The predictive value of MGMT gene promoter methylation is being validated in ongoing trials aiming at overcoming this resistance by a dose-dense continuous temozolomide administration or in combination with MGMT inhibitors. Understanding of molecular mechanisms allows for rational targeting of specific pathways of repair, signaling, and angiogenesis. The addition of tyrosine kinase inhibitors vatalanib (PTK787) and vandetinib (ZD6474), the integrin inhibitor cilengitide, the monoclonal antibodies bevacizumab and cetuximab, the mammalian target of rapamycin inhibitors temsirolimus and everolimus, and the protein kinase C inhibitor enzastaurin, among other agents, are in clinical investigation, building on the established chemoradiotherapy regimen for newly diagnosed glioblastoma.
Keywords
Animals, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Brain Neoplasms/drug therapy, Brain Neoplasms/radiotherapy, Combined Modality Therapy, Glioma/drug therapy, Glioma/radiotherapy, Humans
Pubmed
Web of science
Create date
28/01/2008 9:39
Last modification date
20/08/2019 16:46