内分泌
词汇介绍
拓展阅读
解析
temozolomide
释 义 替莫唑胺
例 句 At recurrence temozolomide is effective for anaplastic tumors; well-tolerated and probably equally effective is PCV used as adjuvant therapy. 对于复发的病人，替莫唑胺对间变胶质瘤是有效的。作为辅助治疗，它和PCV 方案有同等的效果。
概述
概述
替莫唑胺是一种口服化疗药物。它是一种烷化剂，用于治疗某些脑癌，作为星形细胞瘤的二线治疗和多形性胶质母细胞瘤的一线治疗。
作用机制
替莫唑胺的治疗益处取决于其烷基化/甲基化 DNA的能力，其最常发生在鸟嘌呤残基的N-7或O-6位置。这种甲基化会破坏DNA并引发肿瘤细胞的死亡。然而，一些肿瘤细胞能够修复这种类型的DNA损伤，因此通过O-6-甲基鸟嘌呤-DNA甲基转移酶表达人类编码的蛋白质O6-烷基鸟嘌呤DNA烷基转移酶（AGT），从而降低替莫唑胺的治疗效果。在一些肿瘤中，MGMT的表观遗传沉默基因阻止了这种酶的合成，因此这种肿瘤对替莫唑胺的杀灭更敏感。相反，脑肿瘤中AGT蛋白的存在预示着对替莫唑胺的反应差，并且这些患者从替莫唑胺化疗中获得的益处很少。
适应症
亚硝基脲和丙卡巴肼难治性间变性星形细胞瘤、新诊断的多形性胶质母细胞瘤。
禁忌症
对于对其过敏或类似药物达卡巴嗪的患者禁用替莫唑胺。严重骨髓抑制患者不推荐使用替莫唑胺。
不良反应
最常见的副作用是骨髓抑制。与替莫唑胺相关的最常见的非血液学不良反应是恶心和呕吐，其是自限性的或通过标准止吐疗法容易控制。后者的这些影响通常是轻度至中度（1至2级）。严重恶心和呕吐的发生率约4%。在开始替莫唑胺治疗之前，已经存在或有严重呕吐病史的患者可能需要止吐治疗。替莫唑胺应在禁食状态下给药，至少在饭前1小时。可以在给予替莫唑胺之前或之后施用止吐疗法。替莫唑胺是遗传毒性，具有致畸性和胎儿中毒，故怀孕期间不宜使用。哺乳期妇女应该在接受药物时停止哺乳。替莫唑胺很少会引起急性呼吸衰竭或肝脏损害。
复制标题同期替莫唑胺全脑放疗治疗多灶性和/或多中心性新诊断胶质母细胞瘤
发表时间：2019-10-10
影响指数：1.6
作者： L Lahmi
期刊：J CLIN NEUROSCI
Glioblastoma (GBM) is the most common primary malignant brain tumour in adults, with 3.55 new cases per 100,000 persons per year, adjusted to the European Standard Population. Despite intensive therapeutic options, GBM is a lethal disease associated with a median overall survival (OS) of less than 24 months. GBM appears as contrast-enhanced space-occupying lesions on magnetic resonance imaging (MRI) with irregular boundaries. Central necrosis and perilesional oedema are common. In 2005, a randomized controlled trial showed that radiation therapy (RT) and temozolomide (TMZ) prolonged OS. Since then, this approach has become the standard treatment for healthy adult patients with newly diagnosed GBM. A recent systemic review and meta-analyses stated that the incidence of solitary glioma is 81%. Other older studies showed that 20% of GBM patients had multiple lesions, described as two entities: multifocal and multicentric (M/M) gliomas. Batzdorf and Malamud defined multifocal GBM as a tumour disseminated along established CNS pathways such as white matter fibre tracts, cerebrospinal fluid, or local invasion; and multicentric glioma as widely separated in location and/ or time. The incidences of multifocal and multicentric (M/M) gliomas were 25.4% and 2.4%, respectively. Recent studies showed that M/M GBM cohorts had significantly poor OS compared to unifocal GBM (6 versus 11 months). Thus, M/M GBMs present one of the worst prognoses of GBMs. The management of such an extended disease is therefore a challenge for neurosurgeons and radiation oncologists. Two first line therapeutic options for treating M/M GBM, after biopsy or partial resection, are currently being implemented: long-term TMZ and radiotherapy (Focal or Whole brain). There are no guidelines regarding the optimal management of M/M GBM.
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