期刊
NEURO-ONCOLOGY
卷 12, 期 1, 页码 87-94出版社
DUKE UNIV PRESS
DOI: 10.1093/neuonc/nop017
关键词
erlotinib; glioblastoma; glioma; meningioma; pharmacokinetics
资金
- NABTC [CA62399, CA62422]
- GCRC [M01-RR00079, CA62426, CA62412, CA16672, U01CA62407-08, U01CA6242108, M01 RR03186, U01CA62405, M01-RR00056, U01 CA62399, M01-RR0865]
- [5-U01CA62399-09]
- NATIONAL CANCER INSTITUTE [U01CA062412, U01CA062399, U01CA062421, U01CA062426, U01CA062407, U01CA062422, P30CA016672, U01CA062405, ZIDBC011098] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000865, M01RR000079, M01RR000056, M01RR003186] Funding Source: NIH RePORTER
The objective of this phase I study was to determine the maximal tolerated dose (MTD) of erlotinib in patients with re current malignant gliomas (MGs) or recurrent meningiomas on enzyme-inducing antiepileptic drugs (EIAEDs). Dose escalation was by a standard 3 x 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 11 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据