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 language | English (US) |
|---|---|
| Pages (from-to) | 285-291 |
| Number of pages | 7 |
| Journal | Journal of Clinical Oncology |
| Volume | 28 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 10 2010 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Phase I clinical and pharmacokinetic study of oral sapacitabine in patients with acute leukemia and myelodysplastic syndrome. / Kantarjian, Hagop; Garcia-Manero, Guillermo; O'Brien, Susan; Faderl, Stefan; Ravandi, Farhad; Westwood, Robert; Green, Simon R.; Chiao, Judy H.; Boone, Patricia A.; Cortes, Jorge; Plunkett, William.
In: Journal of Clinical Oncology, Vol. 28, No. 2, 10.01.2010, p. 285-291.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phase I clinical and pharmacokinetic study of oral sapacitabine in patients with acute leukemia and myelodysplastic syndrome
AU - Kantarjian, Hagop
AU - Garcia-Manero, Guillermo
AU - O'Brien, Susan
AU - Faderl, Stefan
AU - Ravandi, Farhad
AU - Westwood, Robert
AU - Green, Simon R.
AU - Chiao, Judy H.
AU - Boone, Patricia A.
AU - Cortes, Jorge
AU - Plunkett, William
PY - 2010/1/10
Y1 - 2010/1/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=74949124273&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=74949124273&partnerID=8YFLogxK
U2 - 10.1200/JCO.2009.25.0209
DO - 10.1200/JCO.2009.25.0209
M3 - Article
C2 - 19933907
AN - SCOPUS:74949124273
VL - 28
SP - 285
EP - 291
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 2
ER -