Homoharringtonine for the treatment of chronic myelogenous leukemia

Alfonso Quintás-Cardama, Jorge Cortes

Research output: Contribution to journalReview article

32 Scopus citations

Abstract

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 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. 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.

Original languageEnglish (US)
Pages (from-to)1029-1037
Number of pages9
JournalExpert Opinion on Pharmacotherapy
Volume9
Issue number6
DOIs
StatePublished - Apr 1 2008
Externally publishedYes

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Keywords

  • Chronic myelogenous leukemia
  • Homoharringtonine
  • Omacetaxine mepesuccinate
  • T315I mutation

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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