USE OF ARSENIC TRIOXIDE (AS2O3) IN THE TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA (APE) .2. CLINICAL EFFICACY AND PHARMACOKINETICS IN RELAPSED PATIENTS

The therapeutic effect of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL) was evaluated among 15 APL patient s at relapse after all-trans retinoic acid (ATRA) induced and chemothe rapy maintained complete remission (CW). As2O3 was administered intrav enously at the dose of 10 mg/d. Clinical CR was achieved in nine of 10 (90%) patients treated with As2O3 alone and in the remaining five pat ients treated by the combination of As2O3 and low-dose chemotherapeuti c drugs or ATRA. During the treatment with As2O3, there was no bone ma rrow depression and only limited side effects were encountered. Pharma cokinetic studies, which were performed in eight patients, showed that after a peak level of 5.54 mu mol/L to 7.30 mu mol/L, plasma arsenic was rapidly eliminated, and the continuous administration of As2O3 did not alter its pharmacokinetic behaviors. In addition, increased amoun ts of arsenic appeared in the urine, with a daily excretion accounting for approximately 1% to 8% of the total daily dose administered. Arse nic contents in hair and nail were increased, and the peak content of arsenic could reach 2.5 to 2.7 mu g/g tissue at GR. On the other hand, a decline of the arsenic content in hair and nail was observed after withdrawal of the drug. We conclude that As2O3, treatment is an effect ive and relatively safe drug in APL patients refractory to ATRA and co nventional chemotherapy. (C) 1997 by The American Society of Hematolog y.