title: Phase II study of troxacitabine, a novel dioxolane nucleoside analog, in patients with refractory leukemia.
abstract: OBJECTIVE
  To investigate the activity of a novel dioxolane L-nucleoside analog, troxacitabine (L-(-)-OddC, BCH-4556), in patients with refractory leukemia.
  
  
  METHODS
  Study participants were patients with refractory or relapsed acute myeloid (AML) or lymphocytic (ALL) leukemia, myelodysplastic syndromes (MDS), or chronic myelogenous leukemia in blastic phase (CML-BP). Troxacitabine was provided as an intravenous infusion for more than 30 minutes daily for 5 days at a dose of 8.0 mg/m(2)/d (40 mg/m(2) per course). Courses were given every 3 to 4 weeks according to antileukemic efficacy.
  
  
  RESULTS
  Forty-two patients (AML, 18 patients; MDS, one patient; ALL, six patients; CML-BP, 17 patients) were treated. Median age was 51 years (range, 23 to 80 years); 22 patients were male. Stomatitis was the most significant adverse event, with three patients (7%) and two patients (5%), respectively, experiencing grade 3 or 4 toxicity. Ten patients (24%) had grade 3 hand-foot syndrome, and two patients (5%) had grade 3 skin rash. One patient (2%) had grade 3 fatigue and anorexia. Marrow hypoplasia occurred between days 14 and 28 in 12 (75%) of 16 assessable patients with AML. Two complete remissions and one partial remission (18%) were observed in 16 assessable patients with AML. None of six patients with ALL responded. Six (37%) of 16 assessable patients with CML-BP experienced a return to chronic-phase disease.
  
  
  CONCLUSIONS
  Troxacitabine has significant antileukemic activity in patients with AML and CML-BP.
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. fgiles@mdanderson.org
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.forename: Sharyn D
authors.initials: SD
authors.lastname: Baker
authors.forename: Carol B
authors.initials: CB
authors.lastname: Miller
authors.forename: Susan M
authors.initials: SM
authors.lastname: O'Brien
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Thomas
authors.forename: Michael
authors.initials: M
authors.lastname: Andreeff
authors.forename: Carol
authors.initials: C
authors.lastname: Bivins
authors.forename: Jacques
authors.initials: J
authors.lastname: Jolivet
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003596:Cytosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004148:Dioxolanes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D007951:Leukemia, Myeloid / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy; D012074:Remission Induction
chemical_list: D000970:Antineoplastic Agents; D004148:Dioxolanes; C074908:troxacitabine; D003596:Cytosine