Arsenic trioxide dose capping to decrease toxicity in the treatment of acute promyelocytic leukemia. (September 2022)

• Record Type: Journal Article
• Authors: Zacholski, Kyle; Hambley, Bryan; Hickey, Erin; Kashanian, Sarah; Li, Andrew; Baer, Maria R; Duong, Vu H; Newman, Matthew J; DeZern, Amy; Gojo, Ivana; Smith, B Douglas; Levis, Mark J; Varadhan, Ravi; Gehrie, Eric; Emadi, Ashkan; Ghiaur, Gabriel
• Is Part Of: Journal of oncology pharmacy practice. Volume 28:Number 6(2022)
• Page Start: 1340
• Page End: 1349
• Publication Date: 2022-09
• Subjects: Acute promyelocytic leukemia -- arsenic trioxide -- obesity -- toxicity -- capped dose; Cancer -- Chemotherapy -- Periodicals; Clinical pharmacology -- Periodicals; 616.994061
• DOI: 10.1177/10781552211024727
• Languages: English
• ISSNs: 1078-1552

Abstract

Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) combination therapy yields high complete remission and disease-free survival rates in acute promyelocytic leukemia (APL). ATO is dosed on actual body weight and high ATO doses in overweight patients may contribute to increased toxicity. We performed a retrospective, two-center study comparing toxicities in patients who received the Lo-Coco et al ATRA/ATO regimen with capped ATO, ≤10 mg/dose, and non-capped ATO, >10 mg/dose. A total of 44 patients were included; 15 received doses ≤10 mg and 29 received >10 mg. During induction, there was no difference in the incidence of grade ≥3 hepatotoxicity, grade ≥3 QTc prolongation, neurotoxicity, and cardiac toxicity between groups. In consolidation, patients receiving >10 mg/dose experienced a greater incidence of neurotoxicity (66.7% vs 22.2%; p = 0.046). Capping doses saved $24634.37/patient and reduced waste of partially-used vials. At a median follow-up of 27 months, no disease relapses occurred in either group. This represents an opportunity to improve the safety profile of this highly effective regimen.