Phase I clinical and pharmacokinetic study of oral sapacitabine in patients with acute leukemia and myelodysplastic syndrome

Hagop Kantarjian, Guillermo Garcia-Manero, Susan O'Brien, Stefan Faderl, Farhad Ravandi, Robert Westwood, Simon R. Green, Judy H. Chiao, Patricia A. Boone, Jorge Cortes, William Plunkett

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64 Scopus citations

Abstract

Purpose: Sapacitabine is an oral deoxycytidine nucleoside analog with a unique mechanism of action that is different from cytarabine. Patients and Methods: To define the dose-limiting toxicities (DLT) and maximum-tolerated dose (MTD) of sapacitabine given orally twice daily for 7 days every 3 to 4 weeks, or twice daily for 3 days for 2 weeks (days 1 through 3 and days 8 through 10) every 3 to 4 weeks, in refractory-relapse acute leukemia and myelodysplastic syndrome (MDS). A total of 47 patients were treated in the phase I study that used a classical 3 + 3 design. Sapacitabine was escalated from 75 to 375 mg twice daily for 7 days (n = 35) and from 375 to 475 mg twice daily for 3 days on days 1 through 3 and days 8 through 10. Results: The DLTs with both schedules were gastrointestinal. The MTDs were 375 mg twice daily for 7 days and 425 mg twice daily for 3 days on days 1 through 3 and days 8 through 10. The recommended phase II single-agent dose schedules were 325 mg twice daily for 7 days and 425 mg twice daily for 3 days on days 1 through 3 and days 8 through 10. Responses were observed in 13 patients (28%); four were complete responses, and nine were marrow complete responses. Conclusion: Sapacitabine is a new, safely administered, oral deoxycytidine analog that has encouraging activity in leukemia and MDS. Phase II studies are ongoing.

Original languageEnglish (US)
Pages (from-to)285-291
Number of pages7
JournalJournal of Clinical Oncology
Volume28
Issue number2
DOIs
StatePublished - Jan 10 2010
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kantarjian, H., Garcia-Manero, G., O'Brien, S., Faderl, S., Ravandi, F., Westwood, R., Green, S. R., Chiao, J. H., Boone, P. A., Cortes, J., & Plunkett, W. (2010). Phase I clinical and pharmacokinetic study of oral sapacitabine in patients with acute leukemia and myelodysplastic syndrome. Journal of Clinical Oncology, 28(2), 285-291. https://doi.org/10.1200/JCO.2009.25.0209