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Clin Neurol Neurosurg. 2010 Dec;112(10):876-82. doi: 10.1016/j.clineuro.2010.07.018. Epub 2010 Aug 19.

Mitoxantrone for worsening multiple sclerosis: tolerability, toxicity, adherence and efficacy in the clinical setting.

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1
University of Washington, School of Medicine, Seattle, WA 98195-6465, USA. awundes@u.washington.edu

Abstract

BACKGROUND:

The treatment of worsening Multiple Sclerosis (MS) remains challenging. Mitoxantrone, an anthracyclines, is approved as a treatment for worsening MS. However, systematic analyses of its tolerability and effectiveness outside of controlled trials are few. Certain advantages, including easy application and simple monitoring, need to be balanced against its toxicity.

OBJECTIVE:

To study efficacy, tolerability and feasibility of mitoxantrone treatment in a regular clinical setting.

METHODS:

Retrospective analysis of data from 96 MS patients with worsening MS before, during, and after mitoxantrone. Specifically, we addressed adherence and reasons for deviations from the intended treatment schedule regarding tolerability and safety, and consequences of deviations on clinical efficacy.

RESULTS:

Schedule deviations were frequent. Only a third of patients received the intended cumulative dose. Hematological toxicity was generally mild and transient. In 7 patients, treatment was withheld because of impact on ventricular ejection fraction, in the absence of clinical symptoms of cardiac failure. No malignancies were observed. With respect to clinical benefit, most patients remained stable and the relapse rate decreased with mitoxantrone initiation in both relapsing and secondary MS patients (p<0.0001). A possible modest non-significant dose-effect on annualized relapse rates was observed.

CONCLUSION:

Mitoxantrone may be considered for treatment of refractory MS. Poor tolerability impacted adherence but dose-limiting safety events were rare. Mitoxantrone needs to be carefully assessed in light of recent data on risk of cardiotoxicity and leukemia.

PMID:
20727669
DOI:
10.1016/j.clineuro.2010.07.018
[Indexed for MEDLINE]
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