Novick S C, Warrell R P
Leukemia and Developmental Chemotherapy Services, Memorial Sloan-Kettering Cancer Center, and the Joan and Sanford I. Weill Medical College of Cornell University, New York, NY 10021, USA.
Semin Oncol. 2000 Oct;27(5):495-501.
Arsenic trioxide (AT) has been the object of renewed interest as a therapeutic since studies in China in the late 1980s confirmed its efficacy in the treatment of acute promyelocytic leukemia (APL). These studies have been replicated in the West, with complete remissions achieved in 80% to 90% of patients with refractory or relapsed APL. The drug has been relatively well tolerated. The dose used for treatment of APL (0.15 mg/kg/d) is approximately 50% of the maximum-tolerated dose (MTD). Common side effects have included fatigue, rash, fluid retention, and QTc-interval prolongation on electrocardiogram. A "retinoic acid syndrome," similar in its manifestations to that noted after administration of all-trans retinoic acid (RA), has been observed in APL patients. Recent studies have included dose-ranging trials to determine pharmacokinetics and the optimum schedule of administration, and studies of possible mechanisms of action. Promising future trials include combining AT with RA in the treatment of newly diagnosed APL, and broadening the range of AT therapy to other leukemias, lymphomas, multiple myeloma and some solid tumors.
自20世纪80年代末中国的研究证实三氧化二砷（AT）对急性早幼粒细胞白血病（APL）的治疗有效以来，它再次成为一种备受关注的治疗药物。这些研究在西方得到了重复验证，80%至90%的难治性或复发性APL患者实现了完全缓解。该药物的耐受性相对良好。用于治疗APL的剂量（0.15 mg/kg/天）约为最大耐受剂量（MTD）的50%。常见的副作用包括疲劳、皮疹、液体潴留以及心电图上QTc间期延长。在APL患者中观察到了一种“维甲酸综合征”，其表现与全反式维甲酸（RA）给药后所观察到的相似。最近的研究包括剂量范围试验以确定药代动力学和最佳给药方案，以及对可能的作用机制的研究。未来有前景的试验包括将AT与RA联合用于治疗新诊断的APL，以及将AT治疗的范围扩大到其他白血病、淋巴瘤、多发性骨髓瘤和一些实体瘤。
