A phase I trial of erlotinib in patients with nonprogressive glioblastoma multiforme postradiation therapy, and recurrent malignant gliomas and meningiomas.
A phase I trial of erlotinib in patients with nonprogressive glioblastoma multiforme postradiation therapy, and recurrent malignant gliomas and meningiomas.
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厄洛替尼治疗非进行性多形性胶质母细胞瘤放射治疗后以及复发性恶性胶质瘤和脑膜瘤的 I 期试验。
DOI：
10.1093/neuonc/nop017
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发表时间：
2010
期刊：
影响因子：
15.9
通讯作者：
Cloughesy,
中科院分区：
文献类型：
--
作者：
Raizer,JeffreyJ;Abrey,LaurenE;Lassman,AndrewB;Chang,SusanM;Lamborn,KathleenR;Kuhn,JohnG;Yung,WKAlfred;Gilbert,MarkR;Aldape,KennethD;Wen,PatrickY;Fine,HowardA;Mehta,Minesh;Deangelis,LisaM;Lieberman,Frank;Cloughesy,
这项I期研究的目的是确定厄洛替尼在接受酶诱导抗癫痫药物（EIAED）治疗的复发性恶性胶质瘤（MG）或复发性脑膜瘤患者中的最大耐受剂量（MTD）。剂量递增采用标准3 × 3设计。厄洛替尼的初始起始剂量为每日150 mg。如果未观察到剂量限制性毒性（DLT），则按照以下方式进行剂量递增：200 mg/天、275 mg/天，然后以125 mg增量增加，直至达到MTD。MTD定义为6例患者中≤ 1例发生DLT且上述剂量发生2例或2例以上DLT的剂量。MTD为650 mg/天;在775 mg/天剂量组2例患者中观察到的DLT为3级皮疹。药代动力学分析显示，与我们单独发表的II期数据相比，EIAED对厄洛替尼的代谢有显著影响。主要毒副反应为皮疹和腹泻。厄洛替尼在接受EIAED的患者中的MTD显著高于标准剂量150 mg。这对进一步开发这种药物治疗MG以及对其他恶性肿瘤患者（如正在使用酶诱导药物的NSCLC）进行最佳管理具有重要意义。
The objective of this phase I study was to determine the maximal tolerated dose (MTD) of erlotinib in patients with recurrent malignant gliomas (MGs) or recurrent meningiomas on enzyme-inducing antiepileptic drugs (EIAEDs). Dose escalation was by a standard 3 × 3 design. The initial starting dose of erlotinib was 150 mg daily. If no dose-limiting toxicity (DLT) was observed, then dose escalation occurs as follows: 200 mg/day, 275 mg/day, and then increased in 125 mg increments until the MTD was reached. The MTD was defined as the dose where ≤1 of 6 patients experienced a DLT and the dose above had 2 or more DLTs. The MTD was 650 mg/day; the observed DLTs were grade 3 rash in 2 patients at 775 mg/day. Pharmacokinetic analysis showed a significant influence of EIAEDs on the metabolism of erlotinib when compared with our phase II data published separately. Primary toxicities were rash and diarrhea. The MTD of erlotinib in patients receiving EIAEDs is substantially higher than the standard dose of 150 mg. This has important implications for further development of this drug in the treatment of MG as well as the optimal management of patients with other malignancies such as NSCLC who are on enzyme-inducing drugs.
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影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
影响因子：
158.5
作者：
Mellinghoff, IK;Wang, MY;Mischel, PS
通讯作者：
Mischel, PS
不可切割的突变前蛋白货物对内质网信号肽酶的竞争性抑制
影响因子：
4.8
作者：
Cui, Jingqiu;Chen, Wei;Liu, Ming
通讯作者：
Liu, Ming
影响因子：
2.3
作者：
Ling, Jie;Fettner, Scott;Rakhit, Ashok
通讯作者：
Rakhit, Ashok
影响因子：
4.8
作者：
Nathoo, N;Vogelbaum, MA
通讯作者：
Vogelbaum, MA