Document Detail


Dasatinib: a review of its use in the treatment of chronic myeloid leukaemia and Philadelphia chromosome-positive acute lymphoblastic leukaemia.
MedLine Citation:
PMID:  21902298     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Dasatinib (Sprycel®) is an orally administered small molecule inhibitor of multiple tyrosine kinases, including BCR-ABL and SRC family kinases, which is indicated for the treatment of adults with newly diagnosed chronic-phase chronic myeloid leukaemia (CML), CML (chronic-, accelerated- or blast-phase) with resistance or intolerance to prior therapy, including imatinib, or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) with resistance or intolerance to prior therapy. Dasatinib is ≈325-fold more active than imatinib in inhibiting wild-type ABL kinase in vitro and is active against a wide variety of imatinib-resistant BCR-ABL mutants, except for T315I. This article reviews the efficacy and tolerability of dasatinib in the treatment of patients with newly diagnosed chronic-phase CML or imatinib-resistant or -intolerant CML or Ph+ ALL, as well as summarizing its pharmacological properties. In clinical trials, oral dasatinib was effective in achieving major or complete cytogenetic responses in both newly diagnosed and imatinib-resistant or -intolerant chronic-phase CML. Dasatinib was likewise effective in achieving major or overall haematological responses in imatinib-resistant or -intolerant, accelerated- or blast-phase CML, or Ph+ ALL. Responses were rapidly achieved within 1-3 months and were durable over 1-5 years of follow-up. The majority of adverse events with dasatinib were of mild to moderate severity. Fluid retention (including pleural effusion) was the most common adverse event. Haematological abnormalities were common and cytopenias were the most common grade 3/4 adverse events. Dasatinib 100 mg administered once daily was as effective as dasatinib 70 mg administered twice daily, and was better tolerated, being associated with lower incidences of pleural effusion and grade 3/4 thrombocytopenia, in particular. Dasatinib was more effective than high-dose imatinib in the treatment of patients with imatinib-resistant chronic-phase CML and was more effective than standard dosages of imatinib, as well as being associated with less frequent fluid retention, in patients with newly diagnosed chronic-phase CML. Dasatinib was generally equally effective in patients with or without BCR-ABL mutations at baseline. Therefore, oral dasatinib is a highly effective once-daily therapy for the first-line treatment of newly diagnosed patients with chronic-phase CML, as well as for the treatment of patients with imatinib-resistant or -intolerant chronic- and advanced-phase CML or Ph+ ALL.
Authors:
Paul L McCormack; Susan J Keam
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Drugs     Volume:  71     ISSN:  0012-6667     ISO Abbreviation:  Drugs     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-09     Completed Date:  2011-12-09     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  7600076     Medline TA:  Drugs     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  1771-95     Citation Subset:  IM    
Affiliation:
Adis, a Wolters Kluwer Business, Auckland, New Zealand. demail@adis.co.nz
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MeSH Terms
Descriptor/Qualifier:
Clinical Trials as Topic
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
Philadelphia Chromosome
Protein Kinase Inhibitors / therapeutic use*
Pyrimidines / therapeutic use*
Thiazoles / therapeutic use*
Chemical
Reg. No./Substance:
0/Protein Kinase Inhibitors; 0/Pyrimidines; 0/Thiazoles; RBZ1571X5H/dasatinib
Comments/Corrections
Republished in:
BioDrugs. 2012 Feb 1;26(1):61-4   [PMID:  22233429 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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