Nilotinib: a novel Bcr-Abl tyrosine kinase inhibitor for the treatment of leukemias

Abstract

The successful introduction of the tyrosine kinase inhibitors has initiated a new era in the management of chronic myeloid leukemia (CML). Imatinib mesilate therapy has significantly improved the prognosis of CML. A minority of patients in chronic-phase CML--and more patients in advanced phases--are resistant to imatinib, or develop resistance during treatment. This is attributed, in 40-50% of cases, to the development of mutations in the Bcr-Abl tyrosine kinase domain that impair imatinib binding. Nilotinib (Tasigna) is a novel potent selective oral kinase inhibitor. 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.