title: Omacetaxine mepesuccinate in patients with advanced chronic myeloid leukemia with resistance or intolerance to tyrosine kinase inhibitors.
abstract: Omacetaxine mepesuccinate promotes apoptosis by inhibiting the production of short-lived oncoproteins. The efficacy and safety of omacetaxine in patients with advanced chronic myeloid leukemia (CML) previously treated with tyrosine kinase inhibitors were assessed in two phase II trials (CML-202 and CML-203). Fifty-one patients in accelerated phase (AP-CML) and 44 in myeloid blast phase (BP-CML) received subcutaneous omacetaxine 1.25 mg/m(2) twice daily days 1-14 every 28 days until hematologic response/improvement or any cytogenetic response, then days 1-7 every 28 days until disease progression. The primary endpoint was maintenance or attainment of a major hematologic response (MHR). Cytogenetic responses were also evaluated. MHR was 37% in patients with AP-CML and 9% with BP-CML (22% and 5% in those with a history of T315I). Most grade 3/4 adverse events were related to myelosuppression, and were generally manageable. Omacetaxine demonstrates activity and an acceptable safety profile in pretreated patients with advanced CML, irrespective of mutational status.
authors.affiliation: Emory University School of Medicine , Atlanta, GA , USA.
authors.forename: H Jean
authors.initials: HJ
authors.lastname: Khoury
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Meir
authors.initials: M
authors.lastname: Wetzler
authors.forename: Tamas
authors.initials: T
authors.lastname: Masszi
authors.forename: Raghunadharao
authors.initials: R
authors.lastname: Digumarti
authors.forename: Adam
authors.initials: A
authors.lastname: Craig
authors.forename: Annie-Claude
authors.initials: AC
authors.lastname: Benichou
authors.forename: Luke
authors.initials: L
authors.lastname: Akard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D006248:Harringtonines / Q000627:therapeutic use*; D000077863:Homoharringtonine; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D006248:Harringtonines; D047428:Protein Kinase Inhibitors; D000077863:Homoharringtonine
keywords: Drug resistance; accelerated; blast; myeloid leukemias and dysplasias; omacetaxine; pharmacotherapeutics