Shen Z X, Chen G Q, Ni J H, Li X S, Xiong S M, Qiu Q Y, Zhu J, Tang W, Sun G L, Yang K Q, Chen Y, Zhou L, Fang Z W, Wang Y T, Ma J, Zhang P, Zhang T D, Chen S J, Chen Z, Wang Z Y
Shanghai Institute of Hematology, Department of Hematology, Rui-Jin Hospital, P.R. China.
Blood. 1997 May 1;89(9):3354-60.
The therapeutic effect of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL) was evaluated among 15 APL patients at relapse after all-trans retinoic acid (ATRA) induced and chemotherapy maintained complete remission (CR). As2O3 was administered intravenously 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 patients treated by the combination of As2O3 and low-dose chemotherapeutic drugs or ATRA. During the treatment with As2O3, there was no bone marrow depression and only limited side effects were encountered. Pharmacokinetic studies, which were performed in eight patients, showed that after a peak level of 5.54 micromol/L to 7.30 micromol/L, plasma arsenic was rapidly eliminated, and the continuous administration of As2O3 did not alter its pharmacokinetic behaviors. In addition, increased amounts of arsenic appeared in the urine, with a daily excretion accounting for approximately 1% to 8% of the total daily dose administered. Arsenic contents in hair and nail were increased, and the peak content of arsenic could reach 2.5 to 2.7 microg/g tissue at CR. 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 effective and relatively safe drug in APL patients refractory to ATRA and conventional chemotherapy.
在15例急性早幼粒细胞白血病（APL）患者中评估了三氧化二砷（As2O3）对全反式维甲酸（ATRA）诱导及化疗维持完全缓解（CR）后复发患者的治疗效果。As2O3以10mg/d的剂量静脉给药。单用As2O3治疗的10例患者中有9例（90%）达到临床CR，其余5例患者采用As2O3与小剂量化疗药物或ATRA联合治疗。在As2O3治疗期间，未出现骨髓抑制，仅出现有限的副作用。对8例患者进行的药代动力学研究表明，血浆砷在达到5.54μmol/L至7.30μmol/L的峰值水平后迅速消除，持续给予As2O3并未改变其药代动力学行为。此外，尿中砷含量增加，每日排泄量约占给药总日剂量的1%至8%。头发和指甲中的砷含量增加，在CR时砷的峰值含量可达2.5至2.7μg/g组织。另一方面，停药后观察到头发和指甲中砷含量下降。我们得出结论，As2O3治疗对ATRA和传统化疗难治的APL患者是一种有效且相对安全的药物。
