Homoharringtonine for the treatment of chronic myelogenous leukemia.
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.


CONCLUSIONS
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.
Quintás-Cardama
Alfonso
A
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Unit 428, 1515 Holcombe Blvd., Houston, TX 77030, USA. aquintas@mdanderson.org
Cortes
Jorge
J
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D006248:Harringtonines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077863:Homoharringtonine; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*
D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D006248:Harringtonines; D000077863:Homoharringtonine