Rinsho Shinkeigaku (Clinical Neurology)

Educational Lecture 8

Clinical trial updates for malignant brain tumors

Toshihiko Wakabayashi, M.D., Ph.D.

Department of Neurosurgery, Advanced Clinical Research Center at Nagoya University Graduate School of Medicine

Gliomas account for approximately 40% 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 that include anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic oligoastrocytoma (AOA), and glioblastoma multiforme (GBM) are often resistant to treatment; especially, 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 2006, Temozolomide (TMZ) was certified as the treatment agent for malignant gliomas in 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. Previously, we demonstrated that Interferon-β (IFN-β) markedly enhanced chemosensitivity to TMZ in an in vitro study of human glioma cells; this finding suggested that one of the major mechanisms by which IFN-β enhances chemosensitivity is the downregulation of MGMT transcription via p53 induction. Previously, we tried clinical trial of gene therapy by means of IFN-β gene in order to evaluate the safety, feasibility, and preliminary clinical effectiveness, and reasonable results could be obtained. As a next step, we are conducting a clinical trial study, namely, genomic therapy using with siRNA-MGMT. We hope that these new regimen will be safe and well tolerated, and may prolong survival in patients with GBM.
Full Text of this Article in Japanese PDF (554K)

(CLINICA NEUROL, 51: 853|856, 2011)
key words: Brain Tumor, Image-guided Neurosurgery, Gene-therapy, Genomic therapy, Robotics

(Received: 19-May-11)