Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea.
J Neurooncol. 2013 Apr;112(2):277-83. doi: 10.1007/s11060-013-1060-3. Epub 2013 Feb 2.
The current best standard care for glioblastoma still has limitations and unsatisfactory outcomes in patients with an unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) promoter. Whether the effects of temozolomide are primarily due to its concomitant use with radiotherapy or are also mediated by their independent use in the adjuvant phase remain unclear. To validate the concomitant use of temozolomide in the standard protocol, we compared the overall survival of two prospective patient groups: one treated with radiotherapy alone followed by adjuvant temozolomide (RT → TMZ group) and the other treated with concomitant radiotherapy and temozolomide followed by adjuvant temozolomide (CCRT-TMZ group). Each patient in the RT → TMZ group (n = 25) was matched with two patients in the CCRT-TMZ group (n = 50) with respect to age, extent of resection, MGMT promoter methylation status, and postsurgical performance status to minimize the influence of confounding factors. In patients with MGMT promoter methylation, the CCRT-TMZ group showed superior overall survival (OS; median, 41.0 months) and progression-free survival (PFS; median, 24.0 months) compared with the RT → TMZ group. However, the OS and PFS did not differ between the CCRT-TMZ and the RT → TMZ groups in the patients without MGMT promoter methylation. Although this data is from a retrospective analysis using small number of patients, the study might indicate that concomitant use of temozolomide with radiotherapy is a crucial step in the standard treatment for glioblastoma patients with MGMT promoter methylation. And the use of temozolomide, either concurrently or by adjuvant after radiotherapy, remains a questionable value for those with an unmethylated MGMT promoter.
目前,对于未甲基化 O-6-甲基鸟嘌呤-DNA 甲基转移酶(MGMT)启动子的胶质母细胞瘤患者,标准护理仍存在局限性和不理想的结果。替莫唑胺的作用主要是由于其与放疗同时使用,还是也通过其在辅助阶段的独立使用来介导,仍不清楚。为了验证替莫唑胺在标准方案中的同时使用,我们比较了两个前瞻性患者组的总生存期:一组单独接受放疗后接受辅助替莫唑胺治疗(RT→TMZ 组),另一组接受同时放疗和替莫唑胺治疗后接受辅助替莫唑胺治疗(CCRT-TMZ 组)。RT→TMZ 组中的每位患者(n=25)与 CCRT-TMZ 组中的两位患者(n=50)相匹配,根据年龄、切除范围、MGMT 启动子甲基化状态和术后表现状态进行匹配,以最大程度地减少混杂因素的影响。在 MGMT 启动子甲基化的患者中,CCRT-TMZ 组的总生存期(OS;中位数,41.0 个月)和无进展生存期(PFS;中位数,24.0 个月)均优于 RT→TMZ 组。然而,在没有 MGMT 启动子甲基化的患者中,CCRT-TMZ 组和 RT→TMZ 组之间的 OS 和 PFS 没有差异。尽管这是一项使用小数量患者的回顾性分析,但该研究可能表明替莫唑胺与放疗同时使用是胶质母细胞瘤患者 MGMT 启动子甲基化的标准治疗中的关键步骤。替莫唑胺的使用,无论是同时使用还是放疗后辅助使用,对于未甲基化 MGMT 启动子的患者仍然存在疑问。