title: Nilotinib therapy in chronic myelogenous leukemia: the strength of high selectivity on BCR/ABL.
abstract: Imatinib mesylate is currently the standard therapy for chronic myeloid leukemia (CML) patients. Despite the remarkable results achieved with imatinib, the emergence of resistance to this drug has become a significant problem. Several strategies have been developed to overcome imatinib resistance, including dose escalation of the drug, combination treatments or novel targeted agents. Nilotinib is a second-generation tyrosine kinase inhibitor 30-50 fold more potent than imatinib with high affinity and selectivity on BCR/ABL, active against a wide range of mutant clones, except T315I mutation. Phase II trials of nilotinib showed high activity in imatinib-resistant or intolerant CML patients; front-line treatment of chronic phase Ph+ CML demonstrated rapid and stable cytogenetic responses and increasing molecular responses. We here review the development of nilotinib and the efficacy data in phase II and front-line trials.
authors.affiliation: Department of Cellular Biotechnologies and Hematology, University La Sapienza, Rome, Italy. breccia@bce.uniroma1.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
authors.forename: Giuliana
authors.initials: G
authors.lastname: Alimena
mesh_terms: D000818:Animals; D001549:Benzamides; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004357:Drug Synergism; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib