title: A safety evaluation of omacetaxine mepesuccinate for the treatment of chronic myeloid leukemia.
abstract: BACKGROUND
  Therapy of chronic myeloid leukemia (CML) has been completely transformed by the development of tyrosine kinase inhibitors (TKIs). However, a subset of patients will fail TKI therapy due to resistance or intolerance. Omacetaxine mepesuccinate (OM), a protein translation inhibitor, is currently the only approved therapy that does not directly target the kinase domain. It has activity for CML patients irrespective of the phase or underlying kinase domain mutation status.
  
  
  METHODS
  We searched the MEDLINE database for articles published in English on homoharringtonine or omacetaxine from 1970 to present. This article reviews the pharmacokinetics of OM and its clinical evolution for the treatment of CML pre- and post TKI development. Toxicity profile, drug administration and future directions are also discussed.
  
  
  CONCLUSIONS
  OM represents a unique addition to the CML therapeutic armamentarium with its distinct mechanism of action and activity. The adverse event profile is manageable and with subcutaneous administration at the approved dose, cardiac toxicity is no longer a concern. The recent approval of home administration will facilitate access to this therapy and increase patient compliance. We conclude with specific scenarios where OM use should be considered in CP and AP-CML patients in the era of TKI therapy.
authors.affiliation: a Division of Hematology & HSCT, Department of Oncology , King Abdul Aziz Medical City , Riyadh , Kingdom of Saudi Arabia.
authors.forename: Moussab
authors.initials: M
authors.lastname: Damlaj
authors.affiliation: b Department of Oncology , Princess Margaret Cancer Center , Toronto , Canada.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lipton
authors.affiliation: c Department of Oncology , Sir Mortimer B Davis Jewish General Hospital , Montréal , Canada.
authors.forename: Sarit E
authors.initials: SE
authors.lastname: Assouline
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006248:Harringtonines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077863:Homoharringtonine; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D006248:Harringtonines; D047428:Protein Kinase Inhibitors; D000077863:Homoharringtonine
keywords: Chronic myelogenous leukemia; T315I mutation; omacetaxine mepesuccinate; tyrosine kinase inhibitor