Phase 2 trial of talampanel, a glutamate receptor inhibitor, for adults with recurrent malignant gliomas.
Phase 2 trial of talampanel, a glutamate receptor inhibitor, for adults with recurrent malignant gliomas.
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talampanel（一种谷氨酸受体抑制剂）治疗成人复发性恶性神经胶质瘤的 2 期试验。
DOI：
10.1002/cncr.24957
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发表时间：
2010-04-01
期刊：
影响因子：
6.2
通讯作者：
Fine, Howard A.
中科院分区：
文献类型：
--
作者：
Iwamoto, Fabio M.;Kreisl, Teri N.;Kim, Lyndon;Duic, J. Paul;Butman, John A.;Albert, Paul S.;Fine, Howard A.
胶质瘤细胞分泌谷氨酸并表达AMPA谷氨酸受体，参与恶性胶质瘤的增殖、迁移和神经毒性。Talampanel是一种口服AMPA受体抑制剂，在癫痫和其他神经系统疾病的临床试验中具有优异的CNS穿透性和良好的耐受性。我们进行了一项II期试验，以6个月无进展生存期（PFS6）来评估talampanel对复发性恶性胶质瘤患者的疗效。30例患者（胶质母细胞瘤[GBM] 22例，间变性胶质瘤[AG] 8例，63%为男性），中位年龄为51岁（范围20 ~ 67岁），中位KPS为80。患者对治疗耐受良好，大多数不良事件轻微且可逆；最常见的毒性是疲劳（27%）、头晕（23%）和共济失调（17%）。在GBM层中只有一个部分缓解（5%），而在AG患者中没有。中位随访时间为13个月，28例（93%）患者死亡。最初22例GBM患者的PFS6为4.6%，由于治疗无效，研究提前终止；8例AG患者PFS6为0%。GBM患者的中位PFS为5.9周，AG患者为8.9周。GBM患者的中位总生存期为13周，AG患者的中位总生存期为14个月。Talampanel耐受性良好，但作为单一药物在未选择的复发性恶性胶质瘤中没有显著活性。
Glioma cells secrete glutamate and also express AMPA glutamate receptors, which contribute to proliferation, migration and neurotoxicity of malignant gliomas. Talampanel is an oral AMPA receptor inhibitor with excellent CNS penetration and good tolerability in clinical trials for epilepsy and other neurological disorders. We conducted a phase II trial to evaluate the efficacy of talampanel in patients with recurrent malignant glioma as measured by 6-month progression free survival (PFS6). Thirty patients (22 glioblastomas [GBM], 8 anaplastic gliomas [AG]; 63% men) with median age of 51 years (range, 20 to 67) and median KPS of 80 were included. Patients tolerated treatment well and most adverse events were mild and reversible; the most common toxicities were fatigue (27%), dizziness (23%) and ataxia (17%). There was only one partial response (5%) in the GBM stratum and none among AG patients. With a median follow-up of 13 months, 28 patients (93%) had died. The PFS6 was 4.6% for the initial 22 GBM patients and the study was terminated early due to treatment futility; PFS6 was 0% for 8 AG patients. Median PFS was 5.9 weeks for GBM and 8.9 weeks for AG patients. Median overall survival was 13 weeks for GBM and 14 months for AG patients. Talampanel was well tolerated but had no significant activity as a single agent in unselected recurrent malignant gliomas.
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影响因子：
9.9
作者：
Chappell, AS;Sander, JW;Arroyo, S
通讯作者：
Arroyo, S
影响因子：
45.3
作者：
Grossman, Stuart A.;Ye, Xiaobu;Fine, Howard A.
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Fine, Howard A.
影响因子：
158.5
作者：
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Ryan, G
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15.9
作者：
Lamborn, Kathleen R.;Yung, W. K. Alfred;Prados, Michael D.
通讯作者：
Prados, Michael D.
影响因子：
4.1
作者：
LEVIN, VA;CRAFTS, DC;WILSON, CB
通讯作者：
WILSON, CB