[Chemotherapy for malignant gliomas: an update]

Gliomas account for approximately 30% of all brain tumors and are thus the most common primary tumors of the central nervous system (CNS). Despite treatment with aggressive surgical resection, chemotherapy, and radiotherapy, high-grade (WHO grades III and IV) malignant gliomas, especially glioblastoma (GBM), the most common glioma in adults, kill patients within a median time span of a year after diagnosis. In Japan, alkylating agents such as 1-(4-amino-2-methyl-5-pyridiminyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) and methyl-6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) have been used to treat malignant gliomas for a long time; however, this treatment provides few clinical benefits. Temozolomide (TMZ), an oral alkylating agent, has been demonstrated to possess antitumor activity against malignant gliomas with minimal additional toxicity; furthermore, a previous study found that treatment with TMZ significantly prolonged median survival time. In 2006, TMZ was certified as the treatment agent for malignant gliomas by the National Ministry of Health and Welfare of Japan. It is now used as first-line therapy. However, its clinical outcomes depend on the O6-methylguanine-DNA methyltransferase (MGMT) status, and MGMT modification is one of the key factors to deriving greater clinical benefits in the future. Combination therapy with TMZ and other antitumor drugs, especially anti-vascular endothelial growth factor (VEGF) antibody (Avascin), has been aggressively investigated for treating gliomas. Some of these drugs have been studied in experimental animal models and advanced to clinical trials. These studies suggest that combination therapy with TMZ and other antitumor drugs might further improve the clinical outcome of malignant gliomas as compared to TMZ plus radiotherapy. Based on these data, the next step will be to carry out phase II to III clinical studies to improve treatment of malignant brain tumors further.