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

39 Citations (Scopus)

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

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Azacitidine
Myelodysplastic Syndromes
Appointments and Schedules
Safety
Erythrocyte Transfusion
Platelet Transfusion
DNA
Methyltransferases
Therapeutic Uses
Hematologic Neoplasms
Therapeutics
S Phase
Epigenomics
Half-Life
Publications
Leukemia

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes. / Garcia-Manero, G.; Gore, S. D.; Kambhampati, S.; Scott, B.; Tefferi, Ayalew; Cogle, C. R.; Edenfield, W. J.; Hetzer, J.; Kumar, K.; Laille, E.; Shi, T.; MacBeth, K. J.; Skikne, B.

In: Leukemia, 07.10.2015.

Research output: Contribution to journalArticle

Garcia-Manero, G, Gore, SD, Kambhampati, S, Scott, B, Tefferi, A, Cogle, CR, Edenfield, WJ, Hetzer, J, Kumar, K, Laille, E, Shi, T, MacBeth, KJ & Skikne, B 2015, '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
Garcia-Manero, G. ; Gore, S. D. ; Kambhampati, S. ; Scott, B. ; Tefferi, Ayalew ; Cogle, C. R. ; Edenfield, W. J. ; Hetzer, J. ; Kumar, K. ; Laille, E. ; Shi, T. ; MacBeth, K. J. ; Skikne, B. / Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes. In: Leukemia. 2015.
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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.",
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