Arsenicals in hematologic cancers.
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.
Novick
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SC
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.
Warrell
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RP
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy; D010087:Oxides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide