Omacetaxine mepesuccinate

Medical uses

Omacetaxine/homoharringtonine was indicated for use as a treatment for patients with chronic myeloid leukaemia who are resistant or intolerant of tyrosine kinase inhibitors.

In June 2009, results of a long-term open label Phase II study were published, which investigated the use of omacetaxine infusions in CML patients. After twelve months of treatment, about one third of patients showed a cytogenetic response. A study in patients who had failed imatinib and who had the drug resistant T315I mutation achieved cytogenetic response in 28% of patients and hematologic response in 80% of patients, according to preliminary data.

Phase I studies including a small number of patients have shown benefit in treating myelodysplastic syndrome (MDS, 25 patients) and acute myelogenous leukaemia (AML, 76 patients). Patients with solid tumors did not benefit from omacetaxine.

Adverse effects

By frequency:

Very common (10% frequency):

• Diarrhea
• Myelosuppression†
• Injection site reactions
• Nausea
• Fatigue
• Fever
• Muscle weakness
• Joint pain
• Headache
• Cough
• Hair loss
• Constipation
• Nosebleeds
• Upper abdominal pain
• Pain in the extremities
• Oedema
• Vomiting
• Back pain
• Hyperglycemia, sometimes extreme
• Gout
• Rash
• Insomnia

Common (1–10% frequency):

• Seizures
• Haemorrhage

† Myelosuppression, including: thrombocytopenia, anaemia, neutropenia and lymphopenia, in descending order of frequency.

Omacetaxine mepesuccinate can cause fetal harm when administered to a pregnant woman. Women using HHT should avoid becoming pregnant and also avoid nursing while receiving HHT.

Mechanism of action

Omacetaxine mepesuccinate is a protein translation inhibitor. It inhibits protein translation by preventing the initial elongation step of protein synthesis. It interacts with the ribosomal A-site and prevents the correct positioning of amino acid side chains of incoming aminoacyl-tRNAs. Omacetaxine mepesuccinate acts only on the initial step of protein translation and does not inhibit protein synthesis from mRNAs that have already commenced translation.

References

References

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8. (September 2009). "Effect of low-dose cytarabine, homoharringtonine and granulocyte colony-stimulating factor priming regimen on patients with advanced myelodysplastic syndrome or acute myeloid leukemia transformed from myelodysplastic syndrome". Leukemia & Lymphoma.
9. (June 2011). "Low dose of homoharringtonine and cytarabine combined with granulocyte colony-stimulating factor priming on the outcome of relapsed or refractory acute myeloid leukemia". Journal of Cancer Research and Clinical Oncology.
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11. "SYNRIBOTM (omacetaxine mepesuccinate) drug label". FDA.
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