Preliminary Individualized Chemotherapy for Malignant Astrocytomas Based on O6-Methylguanine-Deoxyribonucleic Acid Methyltransferase Methylation Analysis

• Published in: Neurologia medico-chirurgica Vol. 46; no. 8; pp. 387 - 394
• Main Authors: WATANABE, Takao, KATAYAMA, Yoichi, OGINO, Akiyoshi, OHTA, Takashi, YOSHINO, Atsuo, FUKUSHIMA, Takao
• Format: Journal Article
• Language: English
• Published: Japan The Japan Neurosurgical Society 2006; THE JAPAN NEUROSURGICAL SOCIETY
• Subjects: Adult; Aged; Alkylating Agents - therapeutic use; anaplastic astrocytoma; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Astrocytoma - drug therapy; Astrocytoma - genetics; Astrocytoma - pathology; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Brain Neoplasms - pathology; chemotherapy; Chemotherapy, Adjuvant; DNA Methylation; Female; Gene Expression Regulation, Neoplastic; glioblastoma multiforme; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nitrosourea Compounds - therapeutic use; O-Methylguanine-DNA Methyltransferase - genetics; O6-methylguanine-deoxyribonucleic acid methyltransferase methylation
• ISSN: 0470-8105; 1349-8029
• DOI: 10.2176/nmc.46.387

O6-methylguanine-deoxyribonucleic acid methyltransferase gene (MGMT) methylation is apparently correlated with responsiveness to nitrosourea chemotherapy, suggesting this alkylating agent should be effective against MGMT-methylated tumors. MGMT appears not to be linked to platinum resistance, so platinum chemotherapy should be used for MGMT-unmethylated tumors. This study was a preliminary trial of individualized chemotherapy based on MGMT methylation status in a total of 20 patients with newly diagnosed malignant astrocytomas (9 anaplastic astrocytomas and 11 glioblastomas multiforme). The procarbazine, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-2(2-chloroethyl)-3-nitrosourea, and vincristine (PAV) regimen was administered to seven patients with MGMT-methylated tumors, and the carboplatin and etoposide (CE) regimen was administered to 13 patients with MGMT-unmethylated tumors. Objective response to the PAV therapy was noted in all three patients with measurable residual tumor (2 complete responses and 1 partial response). Five of the seven patients continued to be disease-free after initiation of the PAV therapy. Objective response to the CE therapy was seen in only one of seven patients with measurable residual tumor (1 partial response). Three of the 13 patients were free from progression, whereas the remaining 10 patients showed early progression. The PAV regimen is effective against MGMT-methylated malignant astrocytomas, but the CE regimen is not useful at the given dose and schedule in MGMT-unmethylated tumors.