Watanabe Takao, Katayama Yoichi, Ogino Akiyoshi, Ohta Takashi, Yoshino Atsuo, Fukushima Takao
Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.
Neurol Med Chir (Tokyo). 2006 Aug;46(8):387-93; discussion 393-4. doi: 10.2176/nmc.46.387.
O(6)-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.
O(6)-甲基鸟嘌呤-脱氧核糖核酸甲基转移酶基因（MGMT）甲基化显然与对亚硝基脲化疗的反应性相关，这表明这种烷化剂应对MGMT甲基化肿瘤有效。MGMT似乎与铂耐药性无关，因此铂化疗应用于MGMT未甲基化的肿瘤。本研究是一项基于MGMT甲基化状态的个体化化疗初步试验，共纳入20例新诊断的恶性星形细胞瘤患者（9例间变性星形细胞瘤和11例多形性胶质母细胞瘤）。对7例MGMT甲基化肿瘤患者采用丙卡巴肼、1-(4-氨基-2-甲基-5-嘧啶基)甲基-3-2(2-氯乙基)-3-亚硝基脲和长春新碱（PAV）方案，对13例MGMT未甲基化肿瘤患者采用卡铂和依托泊苷（CE）方案。在所有3例有可测量残留肿瘤的患者中观察到对PAV治疗的客观反应（2例完全缓解和1例部分缓解）。7例患者中有5例在开始PAV治疗后持续无病。在7例有可测量残留肿瘤的患者中，仅1例观察到对CE治疗的客观反应（1例部分缓解）。13例患者中有3例无进展，而其余10例患者出现早期进展。PAV方案对MGMT甲基化的恶性星形细胞瘤有效，但CE方案在给定剂量和疗程下对MGMT未甲基化肿瘤无效。
