Nilotinib: a second-generation tyrosine kinase inhibitor for chronic myeloid leukemia.
Imatinib mesylate is currently the standard of care for chronic myeloid leukemia (CML) patients in early chronic phase. However, the emergence of resistance and intolerance has dampened the enthusiasm for this drug. To overcome this phenomenon, different strategies have been developed, including novel targeted agents. Nilotinib, formerly known as AMN107, is a second-generation tyrosine kinase inhibitor 30-fold more potent than imatinib, with high affinity and selectivity on BCR/ABL, and also 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, whereas front-line treatment of the disease in chronic phase 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. The aim of this review is to evaluate the pharmacology, pharmacokinetic and pharmacodynamic properties of the drug and the recent results of clinical trials performed in patients with CML and Ph+ acute lymphoblastic leukemia (ALL).
Breccia
Massimo
M
Department of Biotechnologies and Hematology, University La Sapienza, Via Benevento 6, 00161 Rome, Italy. breccia@bce.uniroma1.it
Alimena
Giuliana
G
D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib