Mitoxantrone — Drug Monograph
Brand names: Novantrone
Drug class: Topoisomerase Inhibitor
Mechanism of Action
Mitoxantrone is a synthetic anthracenedione that intercalates into DNA and inhibits topoisomerase II, causing DNA strand breaks and cross-links that block DNA and RNA synthesis. Although structurally distinct from the anthracyclines (it lacks the sugar moiety and tetracyclic quinone that drive extensive free-radical generation), it shares their topoisomerase II mechanism while producing comparatively less oxidative stress — the basis for its somewhat lower, but still cumulative and dose-limiting, cardiotoxicity.
FDA Indications
- Acute nonlymphocytic (myeloid) leukemia (ANLL) in adults — in combination with cytarabine for induction
- Advanced hormone-refractory prostate cancer — in combination with corticosteroids for palliation of pain
- Secondary progressive, progressive-relapsing, or worsening relapsing-remitting multiple sclerosis (non-oncologic indication)
Common Side Effects
- Nausea and vomiting
- Alopecia (usually mild)
- Blue-green discoloration of urine, sclera, and other secretions
- Fatigue
- Mucositis/stomatitis
- Amenorrhea
Clinical Pearl
An anthracenedione antineoplastic agent widely utilized in AML induction and salvage regimens (e.g., CLAG-M, MEC). CRITICAL SAFETY: carries a lifetime cumulative dose limit due to severe, potentially irreversible cardiotoxicity (LVEF surveillance mandatory; risk rises sharply beyond ~140 mg/m², and prior anthracycline exposure lowers the ceiling). It distinctly causes a benign blue-green discoloration of urine, sweat, tears, and sclera — a useful point-of-care confirmation of recent dosing…
Related Therapies & Mechanisms
- Etoposide (VePesid) — Topoisomerase Inhibitor · Lymphoma
- Acalabrutinib (Calquence) — Lymphoma
- Alemtuzumab (Campath) — Leukemia
- Bendamustine (Treanda) — Lymphoma