Temozolomide (TMZ)を中心とした悪性神経膠腫化学療法の世界の現状

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  • Chemotherapy for Malignant Glioma; Beyond the Temozolomide Era

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Gliomas account for approximately 30% of all brain tumors and are thus the most common primary tumors of the central nervous system (CNS). High-grade (WHO grades III and IV) malignant gliomas, especially glioblastoma (GBM), the most common glioma in adults, kills patients within a median time span of a year after diagnosis despite treatment with aggressive surgical resection, chemotherapy, and radiotherapy. 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 treatmalignant gliomas for a long time, however, this treatment offered few clinical benefits.Temozolomide (TMZ; Temodal®), an oral alkylating agent, has been demonstrated to possess antitumor activity against malignant gliomas, with minimal additional toxicity; furthermore, in a previous study, treatment with this agent significantly prolonged the 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. And it is now used as the 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 obtain greater clinical benefits in the future.TMZ and other antitumor drugs, especially anti VEGF antibody (Avascin®) and/or BCNU wafer (Gliadel®) combination therapy have been aggressively tried for the treatment of gliomas. Some of them were also observed in an experimental animal model and moved to the clinical trials. These studies suggested that TMZ with other antitumor drugs combination therapy might further improve the clinical outcome in malignant gliomas as compared to TMZ plus radiation therapy.Based upon all these data shown previously, there are now going into the next step to perform the phase II to III clinical study for further improvement against malignant brain tumors.

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