Class
- Antineoplastic agent, immunomodulator
Mitoxantrone
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
Mitoxantrone
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
Mitoxantrone
How Long Until It Works
- MS: Months-years. In trials treated patients had fewer relapses at 1 and 2 years
Mitoxantrone
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
Mitoxantrone
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
Mitoxantrone
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
Mitoxantrone
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
Adverse Effects (AEs)
Mitoxantrone
How Drug Causes AEs
- Most AEs are likely related to affect on DNA synthesis and function and its immunosuppressive effect
Mitoxantrone
Notable AEs
- Arrhythmias or ECG changes, leukopenia, anemia, thrombocytopenia, hepatic enzyme elevations, amenorrhea, nausea, urinary tract infections, anorexia, malaise/fatigue, alopecia, weakness, pharygitis, extravasation at IV sites, peripheral edema, dyspnea, chills, infection. Urine may turn blue-green color
Mitoxantrone
Life-Threatening or Dangerous AEs
- Suppression of left ventricular (LV) ejection fraction can lead to heart failure and death
- Serious infections have occurred in patients developing neutropenia on mitoxantrone
Mitoxantrone
Weight Gain
- Unusual
