- Class: Anthracycline antibiotic (antitumor antibiotic).
- Structure: Semisynthetic derivative of daunorubicin (more lipophilic).
Mechanism of Action (MOA)
- DNA intercalation → inhibits DNA/RNA synthesis.
- Topoisomerase II inhibition → prevents DNA repair → double-strand breaks.
- Free radical generation → oxidative damage to DNA, proteins, membranes.
- More lipophilic than daunorubicin → enhanced cell penetration.
Clinical Uses
- Acute Myeloid Leukemia (AML) – often combined with cytarabine (“7+3” regimen).
- Acute Lymphoblastic Leukemia (ALL) – in some protocols.
- Sometimes in aggressive lymphomas.
Dosing (Adults)
- IV only (lipophilic, so no oral formulation in standard use).
- Induction (AML): 12 mg/m²/day IV for 3 days (commonly with cytarabine 100–200 mg/m²/day continuous infusion for 7 days).
- Pediatric regimens: adjusted by protocol (often lower dose).
- Cumulative lifetime dose limit (due to cardiotoxicity): ~150 mg/m² (lower than doxorubicin).
Toxicities
- Dose-limiting: Myelosuppression (neutropenia, thrombocytopenia).
- Cardiotoxicity (like other anthracyclines): both acute (arrhythmias, myocarditis) and chronic (dose-dependent cardiomyopathy, CHF).
- Mucositis, nausea, vomiting, alopecia.
- Extravasation → severe local tissue necrosis (vesicant).
Monitoring
- CBC (for marrow suppression).
- Ejection fraction (LVEF) → baseline & periodically (risk of cardiomyopathy).
- Liver & renal function (dose adjustments may be needed).
- Watch for extravasation (vesicant precautions).