Troxacitabine-based therapy of refractory leukemia.
Unique among currently approved or in-development nucleoside analogs, troxacitabine (Troxatyl) is an L-nucleoside with significant cytotoxic activity. Its stereochemistry and cellular transport characteristics render it insensitive to some tumor cell mechanisms of resistance to D-nucleosides, such as cytarabine and fludarabine. Troxacitabine's dose-limiting toxicities were mucositis and hand-foot syndrome in patients with refractory leukemia. Three complete and one partial remissions were observed in 30 patients with refractory acute myeloid leukemia on a Phase I study. Significant activity in blastic phase of chronic myeloid leukemia was seen on a Phase II study. Combinations of troxacitabine with ara-C, topotecan and idarubicin are active in patients with refractory acute myeloid leukemia (AML). Phase II studies in patients with refractory lymphoproliferative diseases are ongoing. Troxacitabine merits further study in patients with hematological malignancies.
Giles
Francis J
FJ
Section of Developmental Thereputics, The University of Texas M.D. Anderson Cancer Center, Department of Lukemia, 1515 Holcombe Boulevard, Box 428, Houston, TX 77030-4095, USA. fgiles@mdanderson.org
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003561:Cytarabine / Q000008:administration & dosage; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004148:Dioxolanes / Q000627:therapeutic use*; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007938:Leukemia / Q000188:drug therapy*; D012074:Remission Induction; D019772:Topotecan / Q000008:administration & dosage
D004148:Dioxolanes; D003561:Cytarabine; C074908:troxacitabine; D019772:Topotecan; D003596:Cytosine; D015255:Idarubicin