Journal
EXPERT OPINION ON PHARMACOTHERAPY
Volume 9, Issue 6, Pages 1029-1037Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/14656566.9.6.1029
Keywords
chronic myelogenous leukemia; homoharringtonine; omacetaxine mepesuccinate; T3151 mutation
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Background: The anticancer activity of the natural alkaloid homoharringtonine (HHT) was first recognized by Chinese investigators. HHT exerts its activity through inhibition of protein synthesis and promotion of apoptosis. Methods: The authors reviewed the most relevant preclinical and clinical studies involving patients with chronic myelogenous leukemia (CML) receiving therapy with either natural HHT or omacetaxine mepesuccinate (Ceflatonin, Myelostat, CGX-653), a semisynthetic subcutaneously bioavailable form of HHT presently under development for the treatment of CML. Results: Prior to the advent of the tyrosine kinase inhibitor (TKI) imatinib mesilate, controlled clinical studies established HHT as the most active therapy in CML after failure of IFN-a for patients who were not candidates for allogeneic stem cell transplantation. Preliminary results from Phase 11 studies suggest that omacetaxine mepesuccinate is active in patients with imatinib-resistant CML, including those carrying the T3151 mutation, which renders imatinib and second-generation TKIs ineffective. Conclusion: These encouraging results have propelled the development of several Phase II/III trials both in Europe and in the US to further delineate the activity of omacetaxine mepesuccinate in patients with CML who are resistant to TKI therapy.
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