Mitoxantrone multiple sclerosis

Pharmacology and Mechanism of Action Mitoxantrone is an anthracenedione antineoplastic that is indicated for multiple sclerosis. The mechanisms of action thought to be important for MS are as follows ... 

Stuve, O., Kita, M., Pelletier, D. et al. Mitoxantrone as a potential therapy for primary progressive multiple sclerosis. Mult. Scler. 10(Suppl 1) S58-S61,2004. 

Myocardial toxicity, manifested in its most severe form by potentially fatal CHF, may occur either during therapy with mitoxantrone or months to years after termination of therapy. Mitoxantrone use has been associated with cardiotoxicity this risk increases with cumulative dose. In cancer patients, the risk of symptomatic CHF was estimated to be 2.6% for patients receiving up to a cumulative dose of 140 mg/m. For this reason, monitor patients for evidence of cardiac toxicity and question them about symptoms of heart failure prior to initiation of treatment. Monitor patients with multiple sclerosis (MS) who reach a cumulative dose of 100 mg/m for evidence of cardiac toxicity prior to each subsequent dose. Ordinarily, patients with MS should not receive a cumulative dose greater than 140 mg/m. Active or dormant cardiovascular disease, prior or concomitant radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, or concomitant use of other cardiotoxic drugs may increase the risk of cardiac toxicity. Cardiac toxicity with mitoxantrone may occur at lower cumulative doses whether or not cardiac risk factors are present (see Warnings and Administration.and.Dosage). 

Secondary leukemia Secondary leukemia has been reported in cancer patients and multiple sclerosis patients treated with mitoxantrone. 

Hartung HP, Gonsette R, Konig N, Kwiecinski H, Guseo A, Morrissey SP, Krapf H, Zwinger T, Mitoxantrone in Multiple Sclerosis Study Group (MIMS)l (2002) Mitoxantrone in progressive multiple sclerosis A placebo-controlled, double-blind, randomized, multicenter trial. Lancet 360 2018-2025. 

Mitoxantrone (Novantrone) is supplied for intravenous infusion. To induce remission in acute nonlymphocytic leukemia in adults, the drug is given in a daily dose of 12 mg/m for 3 days as a component of a regimen that also includes cytosine arabinoside. Mitoxantrone also is used in advanced hormone-resistant prostate cancer in a dose of 12 to 14 mg/m every 21 days. Mitoxantrone has been approved by the FDA for the treatment of late-stage, secondary progressive multiple sclerosis. 

Bieledd, B. et al. (2008) Treatment of multiple sclerosis with methylpredni-solone and mitoxantrone modulates the expression of CXC chemokine receptors in PBMC. Journal of Clinical Immunology, 28, 122-130. 

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