[Chemotherapy and targeted treatments in glioblastomas]

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.

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.

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.