Arsenic trioxide

Definition:
Arsenic trioxide (As₂O₃) is a chemotherapeutic agent used primarily to treat acute promyelocytic leukemia (APL)—both newly diagnosed and relapsed/refractory cases—targeting the PML-RARA fusion protein via degradation.

1. Mechanism of Action:
   • Induces apoptosis and differentiation of APL cells by:
     • Degrading PML-RARA oncoprotein.
     • Generating reactive oxygen species (ROS).
     • Disrupting mitochondrial function.
2. Indications:
   • FDA-approved: APL (with ATRA for induction, consolidation, or relapse).
   • Off-label: Investigated in myelodysplastic syndromes (MDS) and multiple myeloma.
3. Dosing & Administration:
   • IV infusion (typically over 1–2 hours).
   • Common regimens:
     • Induction: 0.15 mg/kg daily until bone marrow remission (max 60 doses).
     • Consolidation: 0.15 mg/kg daily for 5 days/week, 5 weeks per cycle.
4. Adverse Effects:
   • Cardiac: QT prolongation (monitor ECG, electrolytes).
   • Hematologic: Differentiation syndrome (treat with steroids).
   • Metabolic: Hyperleukocytosis, hyperglycemia.
   • GI: Nausea, vomiting.
5. Monitoring:
   • ECG (baseline and weekly) for QT interval.
   • Electrolytes (K⁺, Mg²⁺, Ca²⁺).
   • CBC, LFTs, creatinine.
6. Drug Interactions:
   • QT-prolonging drugs (e.g., fluoroquinolones, antiarrhythmics)—avoid concurrent use.
   • Diuretics (risk of electrolyte imbalances).
7. Special Handling:
   • No USP <800> requirement (non-hazardous per NIOSH 2024).

Clinical Pearl:
ATO + ATRA is curative in >90% of APL cases. For relapsed APL, ATO reinduction followed by autologous HSCT is often effective