期刊
CLINICAL CANCER RESEARCH
卷 18, 期 10, 页码 2954-2963出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-11-2873
关键词
-
类别
资金
- Millennium Pharmaceuticals, Inc.
- NIH [U01-CA062487, U01-CA099168, U01-CA70095, U01-CA069853, U01-CA062505, U01-C 062491]
- Institute for Drug Development, Cancer Therapy and Research Center at University of Texas Health Science Center San Antonio, TX: Cancer Center [P30CA054174]
- Johns Hopkins University Cancer Center [P30 CA006973]
- Janssen Global Services
Purpose: The proteasome inhibitor bortezomib undergoes oxidative hepatic metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate bortezomib pharmacokinetics and safety in patients with varying degrees of hepatic impairment, to inform dosing recommendations in these special populations. Experimental Design: Patients received bortezomib on days 1, 4, 8, and 11 of 21-day cycles. Patients were assigned to four hepatic function groups based on the National Cancer Institute Organ Dysfunction Working Group classification. Those with normal function received bortezomib at the 1.3 mg/m(2) standard dose. Patients with severe, moderate, and mild impairment received escalating doses from 0.5, 0.7, and 1.0 mg/m(2), respectively, up to a 1.3 mg/m(2) maximum. Serial blood samples were collected for 24 hours postdose on days 1 and 8, cycle 1, for bortezomib plasma concentration measurements. Results: Sixty-one patients were treated, including 14 with normal hepatic function and 17, 12, and 18 with mild, moderate, and severe impairment, respectively. Mild hepatic impairment did not alter dose-normalized bortezomib exposure (AUC(0-tlast)) or C-max compared with patients with normal function. Mean dose-normalized AUC(0-tlast) was increased by approximately 60% on day 8 in patients with moderate or severe impairment. Conclusions: Patients with mild hepatic impairment do not require a starting dose adjustment of bortezomib. Patients with moderate or severe hepatic impairment should be started at a reduced dose of 0.7 mg/m(2). Clin Cancer Res; 18(10); 2954-63. (C)2012 AACR.
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