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A phase I trial of continuous infusion of the multidrug resistance inhibitor zosuquidar with daunorubicin and cytarabine in acute myeloid leukemia LEUKEMIA RESEARCH Lancet, J. E., Baer, M. R., Duran, G. E., List, A. F., Fielding, R., Marcelletti, J. F., Multani, P. S., Sikic, B. I. 2009; 33 (8): 1055-1061

Abstract

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 2h at a plasma threshold of 132 ng/ml zosuquidar. The recommended phase II dose of zosuquidar is 700 mg/day.

View details for DOI 10.1016/j.leukres.2008.09.015

View details for Web of Science ID 000266759000010

View details for PubMedID 19108889