Document Detail


Nilotinib-associated vascular events.
MedLine Citation:
PMID:  22633167     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Anecdotal evidence suggests that nilotinib therapy may be associated with severe peripheral artery occlusive disease (PAOD). The authors describe the experience at M.D. Anderson Cancer Center regarding vascular events associated with nilotinib therapy in patients with chronic myeloid leukemia. Overall, 5 cases of PAOD were identified among 233 patients, for an incidence of 2%. Nilotinib is a highly selective inhibitor of the inactive conformation of ABL1 kinase. An improved topologic fit to the ABL1 protein-binding surface contributes to its increased potency over imatinib. This higher selectivity in vitro translated to an improved tolerability in vivo. In fact, nilotinib therapy in the frontline phase III ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients) study was associated with an improved toxicity profile compared with that of imatinib. Intriguingly, several cases of severe peripheral artery occlusive disease (PAOD) have been reported among patients treated with nilotinib in small series. We have identified 5 patients with chronic myeloid leukemia (CML) in whom vascular events developed that were likely related to nilotinib therapy among 233 (2%) patients treated at our institution: 1 patient had recurrent Raynaud syndrome, a second patient had recurrent cerebrovascular accidents, and 3 other patients had PAOD (2 of them with other vascular events, including coronary artery disease and pulmonary emboli, respectively). Risk factors for vascular disease were present in only 1 patient with a history of diabetes mellitus. Although the incidence of vascular events is low, this potential complication should be taken into account when selecting nilotinib for the treatment of CML.
Authors:
Alfonso Quintás-Cardama; Hagop Kantarjian; Jorge Cortes
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Publication Detail:
Type:  Case Reports; Journal Article     Date:  2012-05-24
Journal Detail:
Title:  Clinical lymphoma, myeloma & leukemia     Volume:  12     ISSN:  2152-2669     ISO Abbreviation:  Clin Lymphoma Myeloma Leuk     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-08     Completed Date:  2013-05-22     Revised Date:  2013-11-21    
Medline Journal Info:
Nlm Unique ID:  101525386     Medline TA:  Clin Lymphoma Myeloma Leuk     Country:  United States    
Other Details:
Languages:  eng     Pagination:  337-40     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Aged
Benzamides / therapeutic use
Female
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / chemically induced*
Male
Middle Aged
Piperazines / therapeutic use
Pyrimidines / adverse effects*,  therapeutic use
Risk Factors
Vascular Diseases / chemically induced*
Grant Support
ID/Acronym/Agency:
P30 CA016672/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide; 0/Benzamides; 0/Piperazines; 0/Pyrimidines; BKJ8M8G5HI/imatinib

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