Document Detail

Chronic myeloid leukemia therapy: focus on second-generation tyrosine kinase inhibitors.
MedLine Citation:
PMID:  19337199     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Chronic myeloid leukemia, the most common adult leukemia, is characterized by the Ph+ chromosome produced by the fusion of the BCR gene from chromosome 22 and the ABL gene from chromosome 9. Inhibition of the deleterious effects of this potent oncogene by the tyrosine kinase inhibitor (TKI) imatinib has revolutionized care of this disease, but intolerance and resistance does occur.
METHODS: The authors have reviewed both the preclinical and the clinical data concerning second-generation TKIs intended to circumvent or ameliorate issues with imatinib intolerance or resistance.
RESULTS: Two second-generation TKIs, dasatinib and nilotinib, are currently approved by the US Food and Drug Administration. Both have shown significant clinical activity in patients with chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL) who are resistant or intolerant to imatinib or other therapies.
CONCLUSIONS: The TKIs are a superb example of an effective targeted approach for a malignant disease. As more clinical data become available and additional novel agents are developed, specific therapy and dosing strategies for individuals with CML will depend on the status of their disease, the anticipated side effects, and concurrent drug therapy.
K Leigh McFarland; Gene A Wetzstein
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Cancer control : journal of the Moffitt Cancer Center     Volume:  16     ISSN:  1526-2359     ISO Abbreviation:  Cancer Control     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-01     Completed Date:  2009-06-23     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  9438457     Medline TA:  Cancer Control     Country:  United States    
Other Details:
Languages:  eng     Pagination:  132-40     Citation Subset:  IM    
Department of Pharmacy at the H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, USA.
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MeSH Terms
Antineoplastic Agents / therapeutic use*
Clinical Trials as Topic
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
Protein Kinase Inhibitors / therapeutic use*
Protein-Tyrosine Kinases / antagonists & inhibitors
Pyrimidines / therapeutic use
Thiazoles / therapeutic use
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/Antineoplastic Agents; 0/Protein Kinase Inhibitors; 0/Pyrimidines; 0/Thiazoles; EC Kinases; RBZ1571X5H/dasatinib

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