A phase I trial of continuous infusion of the multidrug resistance inhibitor zosuquidar with daunorubicin and cytarabine in acute myeloid leukemia

被引：42

作者：

Lancet, Jeffrey E. ^{[2
]}

Baer, Maria R. ^{[3
]}

Duran, George E.

List, Alan F. ^{[2
]}

Fielding, Robert ^{[4
]}

Marcelletti, John F. ^{[4
]}

Multani, Pratik S. ^{[4
]}

Sikic, Branimir I. ^{[1
]}

机构：

[1] Stanford Univ, Sch Med, Stanford Med Ctr, Div Oncol,Dept Med, Stanford, CA 94305 USA

[2] Univ S Florida, H Lee Moffitt Canc Ctr, Hematol Malignancies Program, Tampa, FL 33682 USA

[3] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA

[4] Kanisa Pharmaceut Inc, San Diego, CA USA

来源：

LEUKEMIA RESEARCH | 2009年 / 33卷 / 08期

关键词：

Acute myeloid leukemia; Multidrug resistance; P-glycoprotein; Zosuquidar; SOUTHWEST-ONCOLOGY-GROUP; POTENT CYCLOPROPYLDIBENZOSUBERANE MODULATOR; RISK MYELODYSPLASTIC SYNDROME; ACUTE MYELOGENOUS LEUKEMIA; EXPRESSING P-GLYCOPROTEIN; INTENSIVE CHEMOTHERAPY; TRIHYDROCHLORIDE LY335979; QUININE IMPROVES; ELDERLY-PATIENTS; DRUG-RESISTANCE;

D O I：

10.1016/j.leukres.2008.09.015

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Zosuquidar is a potent and specific inhibitor of P-glycoprotein (P-gp). In preliminary experiments, blockade of P-gp for at least 12 h was required to reverse daunorubicin resistance. Because of the short half-life of zosuquidar, we performed a phase I trial of this drug as a 72-h infusion (CIV) in 16 patients during leukemic induction with daunorubicin and cytarabine. Study goals were to establish safety and determine the dose required for P-gp inhibition in NK cells and AML blasts. >90% P-gp inhibition was achieved within 2 h at a plasma threshold of 132 ng/ml zosuquidar. The recommended phase II dose of zosuquidar is 700 mg/day. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：1055 / 1061

页数：7

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