R E V I E W Current available therapies and future directions in the treatment of malignant gliomas Annick Desjardins1,2 David A Reardon1,3 James J Vredenburgh1,2 1The Preston Robert Tisch Brain Tumor Center; 2Department of Medicine; 3Department of Surgery, Duke University Medical Center, Durham, NC, USA Correspondence: Annick Desjardins The Preston Robert Tisch Brain Tumor Center, DUMC 3624, Durham, NC 27710, USA Tel +1 919 668 2993 Fax +1 919 684 6674 Email desja002@mc.duke.edu Abstract: The prognosis of patients diagnosed with malignant glioma (MG) remains poor. However, recent advances in neuro-oncology allowing a better understanding of this particular disease have allowed the development of new therapeutics. Many molecular genetic and signal transduction pathway targets have been identiﬁed that are now being investigated. Novel locoregional treatments, as well as strategies to improve regional delivery, are being evaluated. Studies of combinations of these approaches are also underway. In this review, we will discuss the current and future therapies under evaluation for the treatment of malignant gliomas. Keywords: glioma, glioblastoma, targeted therapy, kinase inhibitor Introduction Primary central nervous system (CNS) tumors represent only 1.35% of all cancers and 2.2% of all cancer-related deaths.1 Unfortunately, the prognosis of the most frequent primary CNS tumors, malignant glioma (MG), remains poor. Glial neoplasms represent about 40% of all primary CNS tumors, over three quarters being malignant.2 MG include Word Health Organization (WHO) grade III: anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and anaplastic oligoastrocytoma (AOA); and WHO grade IV: glioblastoma multiforme (GBM), and gliosarcoma.3,4 Despite the current standard treatments for MG including surgical resection, radiation therapy, and chemotherapy, the survival of patients with MG remains dismal, with a median survival of 2 to 3 years for patients with AA and 9 to 12 months for GBM patients.5 Favorable prognostic factors including youth, absent or minimal neurological signs, complete surgical resection, and good performance status have been identiﬁed, but unfortunately, clinical recurrence or progression is nearly universal. For patients with disease recurrence/progression, available systemic chemotherapies offer modest clinical beneﬁt with a 6-month progression-free survival (PFS) of less than 15% for GBM and 31% for AA,6 and a median overall survival (OS) of 25 weeks and 47 weeks for recurrent GBM and AA, respectively.6 In addition to the fatal prognosis, MG affects many patients in their forties and ﬁfties, frequently terminating promising lives pre- maturely and depriving young families of parents and spouses. Clearly, more effective therapies are desperately needed for patients afﬂicted with these tumors. Temozolomide Radiation therapy (RT) has been the standard-of-care for MG until recently, while systemic chemotherapy has had a limited role.7 However, in a recent phase III study, Stupp et al reported results that made temozolomide (TMZ) (Temodar®, Temodal®, Schering-Plough Corporation), a DNA methylator and a second-generation imidazotetrazine derivative, a standard adjuvant chemotherapy for GBM at ﬁrst diag- nosis. Patients were randomized into 2 groups. One group received concurrent RT and daily TMZ at 75 mg/m2, followed by 6 monthly cycles of TMZ (150–200 mg/m2 Biologics: Targets & Therapy 2009:3 15–25 © 2009 Desjardins et al, publisher and licensee Dove Medical Press Ltd.This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. 15