Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Cancer. 2010 Apr 1;116(7):1776-82. doi: 10.1002/cncr.24957.
: Glioma cells secrete glutamate and also express alpha-amino-3-hydroxy-5 methyl-4-isoxazolepropionate (AMPA) glutamate receptors, which contribute to the proliferation, migration, and neurotoxicity of malignant gliomas. Talampanel is an oral AMPA receptor inhibitor with excellent central nervous system penetration and good tolerability in clinical trials for epilepsy and other neurologic disorders.
: A phase 2 trial was conducted to evaluate the efficacy of talampanel in patients with recurrent malignant glioma as measured by 6-month progression-free survival (PFS6).
: Thirty patients (22 with glioblastomas [GBMs] and 8 with anaplastic gliomas [AGs]; 63% men) with median age of 51 years (range, 20-67 years) and a median Karnofsky performance scale 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 1 partial response (5%) reported in the GBM stratum and none among AG patients. At 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; the PFS6 was 0% for 8 AG patients. The median PFS was 5.9 weeks for GBM and 8.9 weeks for AG patients. The median overall survival was 13 weeks for GBM patients and 14 months for AG patients.
: Talampanel was well-tolerated but had no significant activity as a single agent in unselected recurrent malignant gliomas. Cancer 2010. Published 2010 by the American Cancer Society.
神经胶质瘤细胞会分泌谷氨酸，同时也会表达α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）谷氨酸受体，这些受体促进恶性神经胶质瘤的增殖、迁移和神经毒性。他喷他胺是一种口服 AMPA 受体抑制剂，在癫痫和其他神经疾病的临床试验中具有出色的中枢神经系统穿透性和良好的耐受性。
进行了一项 2 期临床试验，以评估他喷他胺在复发性恶性神经胶质瘤患者中的疗效，通过 6 个月无进展生存期（PFS6）来衡量。
30 例患者（22 例胶质母细胞瘤[GBM]和 8 例间变性神经胶质瘤[AG]；63%为男性），中位年龄为 51 岁（范围，20-67 岁），中位 Karnofsky 表现量表评分为 80 分。患者对治疗耐受良好，大多数不良事件为轻度和可逆的；最常见的毒性是疲劳（27%）、头晕（23%）和共济失调（17%）。在 GBM 分层中仅报告了 1 例部分缓解（5%），而 AG 患者中没有。在中位随访 13 个月时，28 例患者（93%）死亡。最初的 22 例 GBM 患者的 PFS6 为 4.6%，由于治疗无效，该研究提前终止；8 例 AG 患者的 PFS6 为 0%。GBM 患者的中位无进展生存期为 5.9 周，AG 患者为 8.9 周。GBM 患者的中位总生存期为 13 周，AG 患者为 14 个月。
他喷他胺耐受良好，但作为单一药物在未选择的复发性恶性神经胶质瘤中没有显著活性。癌症 2010. 2010 年美国癌症协会出版。
