title: Final analysis of the efficacy and safety of omacetaxine mepesuccinate in patients with chronic- or accelerated-phase chronic myeloid leukemia: Results with 24 months of follow-up.
abstract: BACKGROUND
  Omacetaxine, a protein synthesis inhibitor, is indicated in the United States for the treatment of patients with chronic-phase (CP) or accelerated-phase (AP) chronic myeloid leukemia (CML) with resistance and/or intolerance to 2 or more tyrosine kinase inhibitors.
  
  
  METHODS
  The final analysis, with 24 months of follow-up, included additional efficacy and safety analyses to assess the benefit of long-term omacetaxine administration (1.25 mg/m(2) twice daily for 14 days every 28 days followed by 7 days every 28 days) in CP-CML and AP-CML patients receiving >3 cycles.
  
  
  RESULTS
  Eighteen percent of CP-CML patients achieved a major cytogenetic response (MCyR) with a median duration of 12.5 months (95% confidence interval [CI], 3.5 months to not reached [NR]); responses were maintained for ≥12 months in 3 of 14 responders, and the median overall survival (OS) was 40.3 months (95% CI, 23.8 months to NR). Among patients with AP-CML, 14% achieved or maintained a major hematologic response for a median of 4.7 months (95% CI, 3.6 months to NR); MCyR was not achieved, and the median OS was 14.3 months (95% CI, 6.7-18.7 months). In patients with CP-CML and patients with AP-CML who received >3 cycles of treatment (n = 50 and n = 14, respectively), the median OS was 49.3 months (95% CI, 23.8 months to NR) and 24.6 months (95% CI, 12-37.2 months), respectively. Grade 3 or higher hematologic toxicities were the major side effects (79% and 73% for CP-CML and AP-CML, respectively), with discontinuation due to toxicity in 10% of CP patients and in 5% of AP patients.
  
  
  CONCLUSIONS
  These results suggest that the long-term administration of omacetaxine is feasible with dose adjustments to manage toxicities and that omacetaxine provides a durable benefit for some patients.
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Delphine
authors.initials: D
authors.lastname: Rea
authors.forename: Meir
authors.initials: M
authors.lastname: Wetzler
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lipton
authors.forename: Luke
authors.initials: L
authors.lastname: Akard
authors.forename: H Jean
authors.initials: HJ
authors.lastname: Khoury
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.forename: Agnès
authors.initials: A
authors.lastname: Guerci-Bresler
authors.forename: Charles
authors.initials: C
authors.lastname: Chuah
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellmann
authors.forename: Raghunadharao
authors.initials: R
authors.lastname: Digumarti
authors.forename: Purvish M
authors.initials: PM
authors.lastname: Parikh
authors.forename: Laurence
authors.initials: L
authors.lastname: Legros
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Warzocha
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Li
authors.forename: Mihaela
authors.initials: M
authors.lastname: Munteanu
authors.forename: Franck E
authors.initials: FE
authors.lastname: Nicolini
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006248:Harringtonines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077863:Homoharringtonine; D006801:Humans; D015465:Leukemia, Myeloid, Accelerated Phase / Q000188:drug therapy*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D006248:Harringtonines; D047428:Protein Kinase Inhibitors; D000077863:Homoharringtonine; D011505:Protein-Tyrosine Kinases
keywords: T315I; intolerance; protein synthesis inhibitor; resistance; tyrosine kinase inhibitor (TKI)