Studies on the clinical efficacy and pharmacokinetics of low-dose arsenic trioxide in the treatment of relapsed acute promyelocytic leukemia: a comparison with conventional dosage

Abstract

Twenty cases of patients with relapsed acute promyelocytic leukemia (APL) were entered into this study for evaluating the clinical efficacy and pharmacokinetics of low-dose arsenic trioxide (As₂O₃). As₂O₃ was given at a daily dose of 0.08 mg/kg intravenously for 28 days. Pharmacokinetic study was carried out in eight patients. 16/20 (80%) patients achieved CR. The occurrence of some toxic events including gastrointestinal disturbance, facial edema and cardiac toxicity seemed reduced in the low-dose group than those in the standard-dose group. Differentiation changes were observed in peripheral blood, as well as in bone marrow (BM). Pharmacokinetic study showed that the plasma concentration increased soon after administration of As₂O₃ with the peak values of 1.535–3.424 μmol/l. After infusion, the plasma concentration was around 0.1–0.5 μmol/l. The arsenic concentration of the plasma of BM aspirates 24 h after administration in five patients was close to the level needed for differentiation-inducing effect. The estimated 2-year OS and RFS were 61.55 ± 15.79% and 49.11 ± 15.09% respectively, with no difference as compared with those in patients treated with conventional dose (P = 0.2865 and 0.7146, respectively). In conclusion, we demonstrated that low-dose As₂O₃ had the same effect as the conventional dosage and the mechanism of low-dose arsenic seemed to primarily induce differentiation of APL cells.