Omacetaxine for treatment-resistant or treatment-intolerant adult chronic myeloid leukemia.
OBJECTIVE
The pharmacology, pharmacokinetics, clinical efficacy, and safety of a first-in-class protein synthesis inhibitor for use in treatment-resistant chronic myeloid leukemia (CML) are reviewed.


CONCLUSIONS
Omacetaxine mepesuccinate (Synribo, Teva Pharmaceuticals) is a potent plant alkaloid isolated from Cephalotaxus (Chinese yew tree) species. It has a mechanism of action distinct from that of the standard first-line therapy for CML, tyrosine kinase inhibitors (TKIs), and has demonstrated efficacy in adult patients with chronic- or accelerated-phase CML who develop intolerance to two or more TKIs or experience multiple TKI treatment failures. Two open-label Phase II trials (combined n = 108) demonstrated that omacetaxine produced a major cytogenetic response in 18.4% of patients with chronic-phase CML and a major hematologic response in 14.3% of patients with accelerated-phase CML (median duration of reponse, 12.5 and 4.7 months, respectively). Symptom improvement or improved overall survival in omacetaxine-treated patients has not been demonstrated. In clinical trials to date, the most common grade 1-4 adverse reactions included thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, and asthenia. The drug is administered subcutaneously on an intermittent schedule (14 days on, 14 days off during induction; 7 days on, 21 days off during maintenance). Research to better delineate omacetaxine's optimal role in the management of CML and other hematologic malignancies (e.g., acute myelogenic leukemia) is ongoing.


CONCLUSIONS
Omacetaxine, a novel protein synthesis inhibitor, provides an alternative therapy for patients with CML who have experienced TKI treatment failures or are intolerant of two or more TKIs.
Clement Chung, Pharm.D., BCOP, BCPS, is Oncology Clinical Pharmacist, Lyndon B. Johnson General Hospital, Harris Health System, Houston, TX (clement_t_chung@yahoo.com).
Clement
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Chung
D000328:Adult; D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D032483:Cephalotaxus / Q000737:chemistry; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D006248:Harringtonines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000077863:Homoharringtonine; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D006248:Harringtonines; D000077863:Homoharringtonine