Practical management of toxicities associated with tyrosine kinase inhibitors in chronic myeloid leukemia.
The tyrosine kinase inhibitor (TKI) imatinib constitutes the current first-line therapeutic approach for patients with chronic myeloid leukemia. The success of imatinib relies on its potent inhibitory activity against the Bcr-Abl kinase that drives the pathogenesis of this disorder. The vast majority of patients treated with imatinib as a single agent will achieve a complete cytogenetic response. However, a subset of patients will develop imatinib resistance, frequently associated with mutations within the Abl kinase domain. In this setting, treatment with the second-generation TKIs nilotinib and dasatinib has proved highly efficacious. While therapy with these Bcr-Abl TKIs is generally well tolerated, adverse events are common and can result in treatment interruptions that compromise clinical responses. Herein, we discuss some of the toxicities characteristically associated with TKI therapy and provide practical approaches to the clinical management of these adverse effects.
Quintás-Cardama
Alfonso
A
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. aquintas@mdanderson.org
Cortés
Jorge E
JE
Kantarjian
Hagop
H
D001549:Benzamides; D002986:Clinical Trials as Topic; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl; D006402:Hematologic Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D010879:Piperazines / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000009:adverse effects; D013844:Thiazoles / Q000009:adverse effects
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib; D000069439:Dasatinib