Multicenter evaluation of arsenic trioxide dosing in obese patients with low–intermediate risk acute promyelocytic leukemia

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

“…In the current study, three obese patients received capped doses to 10 mg, which may have balanced the increased risk of toxicity in obese patients that has been previously reported. 7–9…”

“…15 There were no statistically significant differences in toxicity seen between patients stratified by obesity status, as compared to previous literature which identified that obese patients were more likely have ATO doses held due to adverse events than non-obese patients. 9 The previous study also utilized the WHO class II obesity (BMI 35 kg/m 2 ) and class III (BMI 40 kg/m 2 ) for analysis, as compared to the class I obesity (BMI 30 kg/m 2 ) definition used in this analysis. In the current study, three obese patients received capped doses to 10 mg, which may have balanced the increased risk of toxicity in obese patients that has been previously reported.…”

“…8 Furthermore, a retrospective, cohort analysis of low- and intermediate-risk APL patients found that when ATO was dosed according to ABW with no maximum, obese patients experienced significantly more doses held due to toxicity than non-obese patients. 9 Pharmacokinetic data may provide a rationale for increased toxicity in obese patients. ATO has a volume of distribution of 5.6 L/kg, suggesting that larger individuals have wider drug distribution.…”

Arsenic toxicity manifesting as profuse watery diarrhea during induction therapy for acute promyelocytic leukemia

“…Within the context of APL therapy, underlying comorbidities may also potentially contribute to an increased risk of ATO toxicity. In one retrospective study of low‐to‐intermediate risk APL patients receiving ATO, obese patients with a BMI >/= 35 kg/m 2 were found to have a higher rate of dose holding or modifications due to AEs compared to patients with BMI <35 kg/m 2 , 9 highlighting the need for additional studies of dosing in this population since ATO is currently dosed based on ABW. In addition, patients with mild to severe acute kidney injury (AKI) have demonstrated decreased urinary excretion of ATO and its metabolites, with 1.4‐ to eightfold increased exposure after a multidose administration 10 …”

Old dog, new trick: Trivalent arsenic as an immunomodulatory drug

“…Notably, the use of arsenic derivatives is highly embryotoxic and is contraindicated at any stage of pregnancy (Sanz et al, 2019), while As 2 O 3 at 0.15 mg·kg −1 ·day −1 (standard dose) was well tolerated by paediatric patients with APL and achieved satisfactory outcomes in clinical trials (Kutny et al, 2017). The dose of As 2 O 3 in elderly and obese patients may need to be attenuated while no consensus has been published due to limited experience (Hickey et al, 2019; Lengfelder, Hofmann, & Nolte, 2013).…”