Pharmacokinetics and excretion of 14C-omacetaxine in patients with advanced solid tumors

Cynthia M. Nijenhuis, Edward Hellriegel, Jos H. Beijnen, Diane Hershock, Alwin D.R. Huitema, Luc Lucas, Marja Mergui-Roelvink, Mihaela Munteanu, Laura Rabinovich-Guilatt, Philmore Robertson, Hilde Rosing, Ofer Spiegelstein, Jan H.M. Schellens

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2 Scopus citations


Background Omacetaxine mepesuccinate is indicated in adults with chronic myeloid leukemia resistant and/or intolerant to ≥ 2 tyrosine kinase inhibitor treatments. This phase I study assessed the disposition, elimination, and safety of 14C-omacetaxine in patients with solid tumors. Methods The study comprised a 7-days pharmacokinetic assessment followed by a treatment period of ≤ six 28-days cycles. A single subcutaneous dose of 1.25 mg/m2 14C-omacetaxine was administered to six patients. Blood, urine, and feces were collected through 168 h or until radioactivity excreted within 24 h was <1 % of the dose. Total radioactivity (TRA) was measured in all matrices and concentrations of omacetaxine, 4′-desmethylhomoharringtonine (4′-DMHHT), and cephalotaxine were measured in plasma and urine. For each treatment cycle, patients received 1.25 mg/m2 omacetaxine twice daily for 7 days. Results Mean TRA recovered was approximately 81 % of the dose, with approximately half of the radioactivity recovered in feces and half in urine. Approximately 20 % of the dose was excreted unchanged in urine; cephalotaxine (0.4 % of dose) and 4′ DMHHT (9 %) were also present. Plasma concentrations of TRA were higher than the sum of omacetaxine and known metabolites, suggesting the presence of other 14C-omacetaxine-derived compounds. Fatigue and anemia were common, consistent with the known toxicity profile of omacetaxine. Conclusion Renal and hepatic processes contribute to the elimination of 14C-omacetaxine-derived radioactivity in cancer patients. In addition to omacetaxine and its known metabolites, other 14C-omacetaxine-derived materials appear to be present in plasma and urine. Omacetaxine was adequately tolerated, with no new safety signals.

Original languageEnglish (US)
Pages (from-to)565-574
Number of pages10
JournalInvestigational New Drugs
Issue number5
Publication statusPublished - Oct 1 2016


All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

Cite this

Nijenhuis, C. M., Hellriegel, E., Beijnen, J. H., Hershock, D., Huitema, A. D. R., Lucas, L., ... Schellens, J. H. M. (2016). Pharmacokinetics and excretion of 14C-omacetaxine in patients with advanced solid tumors. Investigational New Drugs, 34(5), 565-574.