• Alfonso Quintás-Cardama and Jorge Cortes.
• Department of Leukemia, The University of Texas MD Anderson Cancer Center, Unit 428, 1515 Holcombe Blvd., Houston, TX 77030, USA. aquintas@mdanderson.org
• Expert Opin Pharmacother. 2008 Apr 1; 9 (6): 1029-37.

BackgroundThe 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.MethodsThe 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.ResultsPrior 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 II studies suggest that omacetaxine mepesuccinate is active in patients with imatinib-resistant CML, including those carrying the T315I mutation, which renders imatinib and second-generation TKIs ineffective.ConclusionThese 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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