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

AbstractPURPOSE:
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.
AuthorsHagop 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
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 28 Issue 2 Pg. 285-91 (Jan 10 2010) ISSN: 1527-7755 [Electronic] United States
PMID19933907 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Arabinonucleosides
  • Cytosine
  • sapacitabine
Topics
  • Acute Disease
  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents (pharmacokinetics, therapeutic use)
  • Arabinonucleosides (administration & dosage, adverse effects)
  • Cytosine (administration & dosage, adverse effects, analogs & derivatives)
  • Drug Administration Schedule
  • Humans
  • Leukemia (drug therapy)
  • Maximum Tolerated Dose
  • Middle Aged
  • Myelodysplastic Syndromes (drug therapy)
  • Survival Analysis

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