Arsenic trioxide dose capping to decrease toxicity in the treatment of acute promyelocytic leukemia

J Oncol Pharm Pract. 2022 Sep;28(6):1340-1349. doi: 10.1177/10781552211024727. Epub 2021 Jun 17.

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.

Keywords: Acute promyelocytic leukemia; arsenic trioxide; capped dose; obesity; toxicity.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols
  • Arsenic Trioxide / adverse effects
  • Arsenicals* / adverse effects
  • Humans
  • Leukemia, Promyelocytic, Acute* / drug therapy
  • Oxides / adverse effects
  • Retrospective Studies
  • Treatment Outcome
  • Tretinoin / adverse effects

Substances

  • Arsenicals
  • Oxides
  • Tretinoin
  • Arsenic Trioxide