Clinical use of intermediate to high dose of N4-behenoyl-1-beta-D-arabinofuranosylcytosine in children with acute leukemia

N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC) is one of the ara-C derivatives resistant to deamination. Administration of BH-AC in an intermediate (500 mg/m2) or a high dose (1000 mg/m2) resulted in maximum BH-AC plasma levels that were 10 to 20 times as high as those obtained at the conventional BH-AC dose and prolonged maintenance of comparatively high levels. High concentrations of ara-C in the plasma were observed just after BH-AC administration and at 24 hours were proportionally far higher than the ratio between the BH-AC doses administered in this study and those usually administered. To prevent the occurrence of shock, which has reportedly occurred in other studies, because of the presence of HCO-60, hydrocortisone was administered together with BH-AC in this study. In the two patients studied, no shock was observed and the only side effects were transient nausea and vomiting. The results suggest that administration of intermediate and high doses of BH-AC, accompanied by HDC, will prove a safe, effective means of enhancing the efficacy of leukemia therapy.
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