Talampanel With Standard Radiation and Temozolomide in Patients With Newly Diagnosed Glioblastoma: A Multicenter Phase II Trial
Talampanel With Standard Radiation and Temozolomide in Patients With Newly Diagnosed Glioblastoma: A Multicenter Phase II Trial
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DOI：
10.1200/jco.2008.21.6895
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发表时间：
2009-09-01
影响因子：
45.3
通讯作者：
Fine, Howard A.
中科院分区：
文献类型：
--
作者：
Grossman, Stuart A.;Ye, Xiaobu;Fine, Howard A.
目的最近的研究表明，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。Talampanel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。患者和方法本试验旨在评估在标准放疗（RT）和替莫唑胺（TMZ）之外接受talampanel治疗的新诊断成胶质细胞瘤成人患者的总生存率。第二个目的是评估在这种情况下的talampanel毒性。Talampanel开始使用RT + TMZ，并因毒性或疾病进展而停用。生存率与历史对照进行比较。结果2005年12月至2006年7月共入组72例患者。他们的中位年龄为60岁（范围为37 - 85岁，17%为70岁），Karnofsky评分中位数为90分（范围为70 - 100分），77%的患者接受了减脂手术。中位随访时间为18个月，55例患者（76%）死亡，中位生存时间为18.3个月（95% CI， 14.6至22.5个月）。当60例18 ~ 70岁的患者与欧洲癌症研究与治疗组织（EORTC）的RT + TMZ数据进行比较时，中位生存期（分别为20.3 v 14.6个月）和24个月生存率（分别为41.7% v 26.5%, P = 0.02）似乎更优越。o -6-甲基鸟嘌呤- dna甲基转移酶甲基化的患者比例低于EORTC研究（分别为29%和43%）。Talampanel耐受性良好，不会增加TMZ已知的血液学或非血液学毒性。结论talampanel可用于RT + TMZ，且无明显的附加毒性。甲基化和非甲基化患者的令人鼓舞的生存结果表明，阻断AMPA受体可能是新诊断的胶质母细胞瘤的有用策略。
PurposeRecent 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.Patients and MethodsThis 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.ResultsSeventy-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.ConclusionTalampanel 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.