Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes

G. Garcia-Manero, S. D. Gore, S. Kambhampati, B. Scott, Ayalew Tefferi, C. R. Cogle, W. J. Edenfield, J. Hetzer, K. Kumar, E. Laille, T. Shi, K. J. MacBeth, B. Skikne

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

CC-486, the oral formulation of azacitidine (AZA), is an epigenetic modifier and DNA methyltransferase inhibitor in clinical development for treatment of hematologic malignancies. CC-486 administered for 7 days per 28-day treatment cycle was evaluated in a phase 1 dose-finding study. AZA has a short plasma half-life and DNA incorporation is S-phase-restricted; extending CC-486 exposure may increase the number of AZA-affected diseased target cells and maximize therapeutic effects. Patients with lower-risk myelodysplastic syndromes (MDS) received 300 mg CC-486 once daily for 14 days (n=28) or 21 days (n=27) of repeated 28-day cycles. Median patient age was 72 years (range 31–87) and 75% of patients had International Prognostic Scoring System Intermediate-1 risk MDS. Median number of CC-486 treatment cycles was 7 (range 2–24) for the 14-day dosing schedule and 6 (1–24) for the 21-day schedule. Overall response (complete or partial remission, red blood cell (RBC) or platelet transfusion independence (TI), or hematologic improvement) (International Working Group 2006) was attained by 36% of patients receiving 14-day dosing and 41% receiving 21-day dosing. RBC TI rates were similar with both dosing schedules (31% and 38%, respectively). CC-486 was generally well-tolerated. Extended dosing schedules of oral CC-486 may provide effective long-term treatment for patients with lower-risk MDS.Leukemia advance online publication, 5 February 2016; doi:10.1038/leu.2015.265.

Original languageEnglish (US)
JournalLeukemia
DOIs
StateAccepted/In press - Oct 7 2015

    Fingerprint

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Garcia-Manero, G., Gore, S. D., Kambhampati, S., Scott, B., Tefferi, A., Cogle, C. R., Edenfield, W. J., Hetzer, J., Kumar, K., Laille, E., Shi, T., MacBeth, K. J., & Skikne, B. (Accepted/In press). Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes. Leukemia. https://doi.org/10.1038/leu.2015.265