- Class: Anthracenedione (synthetic antineoplastic agent).
- Related to: Anthracyclines (doxorubicin, daunorubicin) but modified to reduce free radical–mediated cardiotoxicity.
Mechanism of Action (MOA)
- DNA intercalation → disrupts DNA & RNA synthesis.
- Topoisomerase II inhibitor → prevents DNA repair → double-strand breaks.
- Generates fewer oxygen free radicals than anthracyclines → slightly less cardiotoxicity, but still significant.
Clinical Uses
- Acute Myeloid Leukemia (AML) (esp. relapsed/refractory, sometimes in induction or salvage regimens).
- Prostate cancer (hormone-refractory, palliative).
- Breast cancer (metastatic).
- Non-Hodgkin lymphoma (in some regimens).
- Multiple sclerosis (MS) – approved for secondary progressive, progressive-relapsing, and worsening relapsing-remitting MS (but limited due to cardiotoxicity and leukemia risk).
Dosing (Adults)
- AML induction: 12 mg/m²/day IV × 3 days (combined with cytarabine).
- Prostate cancer (HRPC): 12–14 mg/m² IV q21 days.
- MS: 12 mg/m² IV q3 months (max cumulative dose 140 mg/m² due to cardiotoxicity).
Toxicities
- Dose-limiting: Myelosuppression (neutropenia).
- Cardiotoxicity (CHF, LVEF decline, especially at cumulative dose >140 mg/m²).
- Nausea, vomiting, alopecia (less than anthracyclines).
- Mucositis, diarrhea.
- Blue-green discoloration of urine, sclera, and skin (benign, but noticeable).
- Secondary AML/MDS risk (esp. in MS patients).
Monitoring
- CBC with differential (myelosuppression).
- Ejection fraction (LVEF) before and during therapy.
- Liver function (metabolized hepatically).
- Watch cumulative dose (≤140 mg/m²)
Summary
Mitoxantrone is a synthetic anthracenedione with a mechanism like anthracyclines but somewhat less free radical–mediated toxicity. It’s used in AML, prostate cancer, breast cancer, and MS, with myelosuppression and cardiotoxicity as key concerns.