Troxacitabine Activity in Extramedullary Myeloid Leukemia

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Abstract
Troxacitabine is a novel l-enantiomer nucleoside analog with unique properties in terms of its structure, pharmacokinetics, intracellular transport, and susceptibility to mechanisms of resistance. Troxacitabine has significant activity in patients with refractory myeloid leukemias, both as a single agent and when combined with standard anti-leukemia agents. In a cohort of 170 patients with refractory myeloid leukemia treated with troxacitabine-based regimens on Phase 1 or 2 studies, 10 (6%) had biopsy-proven extramedullary disease, either with or without bone marrow involvement. Six of these patients who received single-agent troxacitabine, 4 received a combination of troxacitabine and cytarabine. Complete response and disappearance of all extramedullary lesions were observed in 6 (60%) of these 10 patients. Two of the 6 responding patients relapsed within 3 months, 2 patients had remissions of 8 and 9 months duration, respectively, 1 patient is in on-going remission at 3, and 1 patient is lost to follow-up. Troxacitabine-based therapy had significant antileukemic activity in extramedullary myeloid leukemias and warrants further investigation in this clinical situation.

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