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Development and targeted use of nilotinib in chronic myeloid leukemia

Authors Carmen Fava, Hagop Kantarjian, Jorge Cortes, Elias Jabbour

Published Date November 2008 Volume 2008:2 Pages 233—243

DOI http://dx.doi.org/10.2147/DDDT.S3181

Published 10 November 2008

Carmen Fava, Hagop Kantarjian, Jorge Cortes, Elias Jabbour

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Abstract: The development of imatinib has resulted in sustained hematologic and cytogenetic remissions in all phases of chronic myeloid leukemia (CML). Despite the high efficacy, relapses have been observed and are much more prevalent in patients with advanced disease. The most common mechanism of acquired resistance has been traced to Bcr-Abl kinase domain mutations. Several strategies have been developed to overcome the problem of imatinib resistance, including imatinib dose escalation, novel targeted agents and combination treatments. A second generation of tyrosine kinase inhibitors was developed, which displays increased potency towards Bcr-Abl and is able to target the majority of CML mutant clones. Nilotinib (Tasigna®, AMN107, Novartis) is a close analog of imatinib with approximately 20-fold higher potency for BCR-ABL kinase inhibition. Preclinical and clinical investigations demonstrate that nilotinib effectively overcomes imatinib resistance, and has induced high rates of hematologic and cytogenetic responses in CML post imatinib failure, with a good tolerance. Nilotinib has been approved for CML patients in chronic and accelerated phases, post imatinib failure.

Keywords: nilotinib, imatinib-resistance, imatinib-intolerance, CML

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Other article by this author:

Nilotinib for the treatment of chronic myeloid leukemia: An evidence-based review

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