Mitoxantrone

• 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.