Mason Warren P, Cairncross J Gregory
Princess Margaret Hospital, Toronto, Ontario, Canada.
Nat Clin Pract Neurol. 2005 Dec;1(2):88-95. doi: 10.1038/ncpneuro0045.
Glioblastoma multiforme is the most common primary brain tumor in adults. Until recently, the standard of care consisted of maximal surgical resection followed by external beam radiotherapy. The role of adjuvant chemotherapy for newly diagnosed glioblastoma has been controversial; most of the numerous randomized phase III trials conducted over the past 40 years have failed to show a statistically significant and clinically meaningful survival advantage for patients randomized to the chemotherapy arm. Consequently, the choices of chemotherapeutics for patients with glioblastoma have been limited, and cytotoxic treatment regimens have usually included a nitrosourea. Temozolomide, a relatively new orally administered methylating agent, has demonstrable activity in glioma. A recent trial conducted under the auspices of the European Organization for the Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) has defined a role for temozolomide in the initial management of glioblastoma. A companion correlative tumor-biology study has identified epigenetic silencing of the promoter of the gene that encodes MGMT (O6-methylguanine-DNA methyltransferase) in tumor specimens as a strong and independent prognostic factor for survival among patients with a newly diagnosed glioblastoma, as well as a predictor of survival benefit from chemoradiotherapy with temozolomide. This review briefly summarizes the development of temozolomide as a therapy for patients with malignant brain tumors, emphasizing recent trials that have established a new standard of care for patients with glioblastoma and speculating on how these advances might influence future therapeutic investigations for malignant primary brain tumors.
多形性胶质母细胞瘤是成人中最常见的原发性脑肿瘤。直到最近，治疗标准包括最大程度的手术切除，随后进行外照射放疗。辅助化疗在新诊断的胶质母细胞瘤中的作用一直存在争议；在过去40年中进行的众多随机III期试验中，大多数都未能显示随机分配到化疗组的患者在统计学上有显著且具有临床意义的生存优势。因此，胶质母细胞瘤患者的化疗药物选择有限，细胞毒性治疗方案通常包括亚硝基脲。替莫唑胺是一种相对较新的口服甲基化剂，在胶质瘤中具有明显的活性。最近由欧洲癌症研究与治疗组织（EORTC）和加拿大国家癌症研究所临床试验组（NCIC CTG）主持进行的一项试验确定了替莫唑胺在胶质母细胞瘤初始治疗中的作用。一项相关的肿瘤生物学研究发现，肿瘤标本中编码MGMT（O6-甲基鸟嘌呤-DNA甲基转移酶）的基因启动子的表观遗传沉默是新诊断胶质母细胞瘤患者生存的一个强大且独立的预后因素，也是替莫唑胺放化疗生存获益的预测指标。本综述简要总结了替莫唑胺作为恶性脑肿瘤患者治疗药物的发展情况，重点介绍了为胶质母细胞瘤患者建立新治疗标准的近期试验，并推测这些进展可能如何影响未来恶性原发性脑肿瘤的治疗研究。
