Troxacitabine-based therapy of refractory leukemia

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Abstract
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.