Mitoxantrone

Therapeutics

Brands

• Novantrone

Generic?

Yes

Class

• Antineoplastic agent, immunomodulator

Commonly Prescribed for

(FDA approved in bold)

• Reducing neurologic disability or relapses in patients with secondary progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (MS)

• Acute nonlymphoblastic leukemia

• Prostate cancer

• Breast cancer

• Non-Hodgkin's lymphoma

How the Drug Works

• A DNA-reactive agent that causes crosslinks and strand breaks, interferes with DNA uncoiling and repair, and has a cytocidal effect on cells. In MS, it appears to blunt the immune processes believed to be responsible in part for the disease

• It suppresses B-cell, T-cell, and macrophage function, impairs antigen proliferation, and decreases the secretion of inflammatory cytokines, including TNFα, IL-2, and interferon gamma, that mediate demyelination

• Due to its slow release from sequestered tissue into blood it is a long-acting immunosuppressant

How Long Until It Works

• MS: Months-years. In trials treated patients had fewer relapses at 1 and 2 years

If It Works

• MS: Continue to use for up to 2-3 years or a total of 140 mg/m² then discontinue because of cardiotoxicity risk

If It Doesn't Work

• For patients failing first-line agents in MS (interferons, glatiramer) and mitoxantrone with frequent relapses (measured by clinical outcome and MRI accumulation of lesions) consider using natalizumab, monthly methylprednisolone, or pulse cyclophosphamide

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Acute attacks in MS are often treated with glucocorticoids, especially if there is functional impairment due to vision loss, weakness, or cerebellar symptoms

• Treat common clinical symptoms with appropriate medication for spasticity (baclofen, tizanidine), neuropathic pain, and fatigue (modafinil)

• Generally not combined with most other MS disease-modifying treatments (natalizumab, interferons, glatiramer) but 1 study showed that adding monthly mitoxantrone to monthly doses of 1 gram methylprednisolone improved outcomes

Tests

• Assess cardiac left ventricular function using echocardiogram or MUGA (multi gated acquisition scan) at baseline and before each dose of mitoxantrone. Obtain a baseline blood count and recheck if symptoms of infection occur

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