Omacetaxine mepesuccinate in chronic myeloid leukemia

Expert Opin Pharmacother. 2014 Nov;15(16):2397-405. doi: 10.1517/14656566.2014.964642.

Abstract

Introduction: Homoharringtonine (HHT) and other alkaloid esters were originally isolated from the Cephalotaxus evergreen tree and have been used in traditional Chinese medicine since the 1970s to treat a variety of malignancies. Although HHT was investigated for the treatment of chronic myeloid leukemia (CML) in the 1990s with good results, the advent of BCR-ABL1 tyrosine kinase inhibitors (TKIs) at that time rapidly established a new standard of care for CML. Omacetaxine mepesuccinate is a semisynthetic derivative of HHT with known clinical activity in relapsed or refractory CML following TKI therapy.

Areas covered: In this review, we summarize the biologic effects of HHT and its derivative, omacetaxine, in CML. Additionally, we analyze the concepts learned from the early trials using these drugs. Data from clinical trials resulting in drug approval are also reviewed.

Expert opinion: Omacetaxine has a clear role in the CML armamentarium for patients in chronic and accelerated phase who have failed or were intolerant to two or more TKIs.

Keywords: chronic myeloid leukemia; homoharringtonine; omacetaxine; tyrosine kinase inhibitor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Harringtonines / pharmacokinetics
  • Harringtonines / therapeutic use*
  • Homoharringtonine
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / pathology

Substances

  • Antineoplastic Agents
  • Harringtonines
  • Homoharringtonine