title: Phase I clinical and pharmacokinetic study of oral sapacitabine in patients with acute leukemia and myelodysplastic syndrome.
abstract: OBJECTIVE
  Sapacitabine is an oral deoxycytidine nucleoside analog with a unique mechanism of action that is different from cytarabine.
  
  
  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.
  
  
  CONCLUSIONS
  Sapacitabine is a new, safely administered, oral deoxycytidine analog that has encouraging activity in leukemia and MDS. Phase II studies are ongoing.
authors.affiliation: The University of Texas M. D. Anderson Cancer Center, Department of Leukemia, Unit 428, 1515 Holcombe Blvd, Houston, TX 77030, USA. hkantarj@mdanderson.org
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Robert
authors.initials: R
authors.lastname: Westwood
authors.forename: Simon R
authors.initials: SR
authors.lastname: Green
authors.forename: Judy H
authors.initials: JH
authors.lastname: Chiao
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Boone
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: William
authors.initials: W
authors.lastname: Plunkett
mesh_terms: D000208:Acute Disease; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D001087:Arabinonucleosides / Q000008:administration & dosage* / Q000009:adverse effects; D003596:Cytosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D003596:Cytosine; C117959:sapacitabine