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.
- Mechanism of Action:
- Induces apoptosis and differentiation of APL cells by:
- Degrading PML-RARA oncoprotein.
- Generating reactive oxygen species (ROS).
- Disrupting mitochondrial function.
- Induces apoptosis and differentiation of APL cells by:
- Indications:
- FDA-approved: APL (with ATRA for induction, consolidation, or relapse).
- Off-label: Investigated in myelodysplastic syndromes (MDS) and multiple myeloma.
- 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.
- Adverse Effects:
- Cardiac: QT prolongation (monitor ECG, electrolytes).
- Hematologic: Differentiation syndrome (treat with steroids).
- Metabolic: Hyperleukocytosis, hyperglycemia.
- GI: Nausea, vomiting.
- Monitoring:
- ECG (baseline and weekly) for QT interval.
- Electrolytes (K⁺, Mg²⁺, Ca²⁺).
- CBC, LFTs, creatinine.
- Drug Interactions:
- QT-prolonging drugs (e.g., fluoroquinolones, antiarrhythmics)—avoid concurrent use.
- Diuretics (risk of electrolyte imbalances).
- 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