Marina Konopleva, Peter F Thall, Cecilia Arana Yi, Gautam Borthakur, Andrew Coveler, Carlos Bueso-Ramos, Juliana Benito, Sergej Konoplev, Yongchuan Gu, Farhad Ravandi, Elias Jabbour, Stefan Faderl, Deborah Thomas, Jorge Cortes, Tapan Kadia, Steven Kornblau, Naval Daver, Naveen Pemmaraju, Hoang Q Nguyen, Jennie Feliu, Hongbo Lu, Caimiao Wei, William R Wilson, Teresa J Melink, John C Gutheil, Michael Andreeff, Elihu H Estey, Hagop Kantarjian
We previously demonstrated vast expansion of hypoxic areas in the leukemic microenvironment and provided a rationale for using hypoxia-activated prodrugs. PR104 is a phosphate ester that is rapidly hydrolyzed in vivo to the corresponding alcohol PR-104A and further reduced to the amine and hydroxyl-amine nitrogen mustards that induce DNA cross-linking in hypoxic cells under low oxygen concentrations. In this phase I/II study, patients with relapsed/refractory acute myeloid leukemia (n=40) after 1 or 2 prior treatments or acute lymphoblastic leukemia (n=10) after any number of prior treatments received PR104; dose ranged from 1...
July 2015: Haematologica