BACKGROUND AND PURPOSE: We review the indications and limitations of 
chemotherapy in glioblastoma multiform (GBM), including the role played by 
alkylating and other cytotoxic agents and the increased input of clinical 
research on targeted agents in GBM management.
METHODS: In 2005, a phase III study clearly concluded in the benefit of adding 
temozolomide during and after radiotherapy treatment in GBM and thus defined the 
new standard of treatment in this devastating disease. This schedule increased 
the median survival from 12.1 to 14 months and the two- and five-year survival 
rates from 8 to 26%, and 3 to 10%, respectively, with a good tolerance profile. 
Moreover, methylation of the promoter of the O6 methylguanine DNA transferase 
(MGMT) gene exhibits a prognostic impact independently of therapeutic schedule 
but may also predict the benefit of adding temozolomide to radiotherapy. 
However, pitfalls in MGMT determination and lack of prospective validation have 
to be solved before considering MGMT as a decisional marker. More recently, 
antiangiogenic agents including enzastaurin, cediranib, bevacizumab, and others 
that target mainly the VEGF pathway, have been evaluated in this highly 
angiogenic disease. Among them, only bevacizumab has been associated with clear 
anti-tumor activity, although the lack of control studies limits the impact of 
the results to date.
CONCLUSIONS: Recent studies conducted in GBM, both in the adjuvant and recurrent 
setting, have changed the natural course of the disease and opened a new area of 
clinical research, including imaging and response evaluation, predictive 
markers, and other targeted therapies.