Mitoxantrone

Mitoxantrone – Clinical Oncology Summary

1) Basic Information

• Drug name: Mitoxantrone

• Drug class: Anthracenedione (Topoisomerase II inhibitor)

• Route: Intravenous (IV) only

• Schedule (SA): S4

• Appearance: Blue solution (may cause blue-green urine)

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2) Indications

Mitoxantrone is used in:

• Metastatic or locally advanced breast cancer

• Non-Hodgkin lymphoma (after failure of first-line therapy)

• Acute myeloid leukaemia (AML) – relapse or induction (with cytarabine)

• Chronic myeloid leukaemia (CML) in blast crisis

• Castrate-resistant (hormone-refractory) prostate cancer

  • Used with prednisone for pain and symptom control (not survival benefit)

⚠️ Not recommended for adjuvant (early-stage) breast cancer

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3) Dosing

Breast cancer / Lymphoma (single agent):

• 14 mg/m² IV every 21 days

• Reduce to 12 mg/m² if poor marrow reserve

AML induction:

• 12 mg/m² IV daily × 5 days

• Often combined with cytarabine

Prostate cancer (CRPC):

• 12–14 mg/m² IV every 21 days

• With prednisone 10 mg daily

⚠️ Lifetime cumulative dose limit:

• 140 mg/m² (cardiotoxicity risk)

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4) Dose Modifications

• Reduce dose based on:

  • Neutropenia

  • Thrombocytopenia

• Withhold treatment if:

  • ANC < 1 500/mm³ (except AML)

• Reduce dose by:

  • 2 mg/m² for moderate myelosuppression

  • 4 mg/m² for severe myelosuppression

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5) Co-medications

Common combinations:

• Cytarabine (AML)

• Cyclophosphamide

• Vincristine

• Prednisone (especially prostate cancer)

• Methotrexate

• Bleomycin

Supportive:

• Antiemetics

• Growth factors (case dependent)

• Infection prophylaxis in high-risk patients

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6) Contraindications

• Hypersensitivity to mitoxantrone

• Pregnancy

• Breastfeeding

• Intrathecal administration (ABSOLUTELY CONTRAINDICATED)

• Severe uncontrolled cardiac disease

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7) Monitoring Requirements

Before and during treatment:

• Full blood count (FBC) – frequent

• LVEF (Echo or MUGA):

  • Baseline

  • Periodically

  • Mandatory if cumulative dose >100 mg/m²

• Liver function tests

• Renal function

• Monitor for:

  • Infection

  • Heart failure symptoms

  • Secondary leukaemia

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8) Side Effects

Common:

• Myelosuppression (neutropenia, anaemia)

• Nausea and vomiting

• Alopecia

• Fatigue

• Blue-green urine (harmless)

Serious:

• Cardiotoxicity → congestive heart failure

• Severe infections / sepsis

• Secondary AML or MDS

• Tumour lysis syndrome (rare)

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9) Drug Interactions

• Increased cardiotoxicity with:

  • Anthracyclines (e.g. doxorubicin)

• Increased myelosuppression with other cytotoxics

• Avoid live vaccines

• Caution with:

  • Anticoagulants (monitor INR)

  • BCRP inhibitors (e.g. gefitinib)

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10) Use in Special Populations

• Elderly: Start at lower dose

• Hepatic impairment: Avoid if significant (clearance reduced)

• Renal impairment: Use with caution

• Pregnancy: Teratogenic

• Fertility:

  • Risk of amenorrhoea

  • Sperm banking advised in men

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11) Duration of Use / When to Stop

Stop treatment if:

• Cumulative dose approaches 140 mg/m²

• Significant drop in LVEF

• Symptomatic heart failure

• Persistent severe myelosuppression

• Disease progression

• Unacceptable toxicity

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https://my-sandoz-com-za-en.cms.sandoz.com/sites/default/files/2023-04/Mitoxantrone-Hexal%20PI.pdf