Grossman Stuart A, Ye Xiaobu, Chamberlain Marc, Mikkelsen Tom, Batchelor Tracy, Desideri Serena, Piantadosi Steven, Fisher Joy, Fine Howard A
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1550 Orleans St, Baltimore, MD 21231, USA.
J Clin Oncol. 2009 Sep 1;27(25):4155-61. doi: 10.1200/JCO.2008.21.6895. Epub 2009 Jul 27.
Recent data suggest that the glutamatergic system is important in the proliferation and migration of glioblastoma. Talampanel is a well-tolerated, oral alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor blocker that could be beneficial in this disease.
This trial was designed to estimate overall survival in adults with newly diagnosed glioblastoma treated with talampanel in addition to standard radiation (RT) and temozolomide (TMZ). A secondary purpose was to evaluate talampanel toxicity in this setting. Talampanel was initiated with RT + TMZ and discontinued for toxicity or disease progression. Survival was compared with historical controls.
Seventy-two patients were enrolled from December 2005 to July 2006. Their median age was 60 years (range, 37 to 85 years, with 17% > 70 years), median Karnofsky performance score was 90 (range, 70 to 100), and 77% had a debulking procedure. With a median follow-up time of 18 months, 55 patients (76%) have died, yielding a median survival time of 18.3 months (95% CI, 14.6 to 22.5 months). When the 60 patients who were 18 to 70 years old were compared with the European Organisation for Research and Treatment of Cancer (EORTC) RT + TMZ data, the median survival (20.3 v 14.6 months, respectively) and percentage of patients surviving at 24 months (41.7% v 26.5%, respectively; P = .02) seemed superior. The percentage of patients methylated at O(6)-methylguanine-DNA methyltransferase was lower than on the EORTC study (29% v 43%, respectively). Talampanel was well tolerated and did not increase the known hematologic or nonhematologic toxicities of TMZ.
Talampanel can be added to RT + TMZ without significant additional toxicity. The encouraging survival results in methylated and unmethylated patients suggest that blocking AMPA receptors may be a useful strategy in newly diagnosed glioblastoma.
近期数据表明，谷氨酸能系统在胶质母细胞瘤的增殖和迁移中起重要作用。他拉莫潘是一种耐受性良好的口服α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体阻滞剂，可能对这种疾病有益。
本试验旨在评估新诊断的胶质母细胞瘤成年患者在接受标准放疗（RT）和替莫唑胺（TMZ）治疗的基础上加用他拉莫潘后的总生存期。次要目的是评估在此情况下他拉莫潘的毒性。他拉莫潘与RT + TMZ同时开始使用，因毒性或疾病进展而停药。将生存期与历史对照进行比较。
2005年12月至2006年7月共纳入72例患者。他们的中位年龄为60岁（范围37至85岁，17%大于70岁），中位卡诺夫斯基功能状态评分90分（范围70至100），77%接受了肿瘤减积手术。中位随访时间为18个月，55例患者（76%）死亡，中位生存期为18.3个月（95%CI，14.6至22.5个月）。将60例年龄在18至70岁的患者与欧洲癌症研究与治疗组织（EORTC）RT + TMZ数据进行比较时，中位生存期（分别为20.3和14.6个月）以及24个月时存活患者的百分比（分别为41.7%和26.5%；P = 0.02）似乎更优。O(6)-甲基鸟嘌呤-DNA甲基转移酶甲基化的患者百分比低于EORTC研究（分别为29%和43%）。他拉莫潘耐受性良好，未增加TMZ已知的血液学或非血液学毒性。
他拉莫潘可添加至RT + TMZ，且无明显额外毒性。甲基化和未甲基化患者令人鼓舞的生存结果表明，阻断AMPA受体可能是新诊断胶质母细胞瘤的一种有用策略。
