Abstract | PURPOSE: 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:
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Authors | 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 |
Journal | Journal 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 |
PMID | 19933907
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Arabinonucleosides
- Cytosine
- sapacitabine
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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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