Mitoxantrone for worsening multiple sclerosis: tolerability, toxicity, adherence and efficacy in the clinical setting.
|Title||Mitoxantrone for worsening multiple sclerosis: tolerability, toxicity, adherence and efficacy in the clinical setting.|
|Publication Type||Journal Article|
|Authors||Wundes A, Kraft GH, Bowen JD, Gooley TA, Nash RA|
|Journal||Clinical Neurology and Neurosurgery|
|Date Published||2010 Dec|
|Adolescent, Adult, Antineoplastic Agents, Blood Cell Count, Clinical Protocols, Disability Evaluation, Disease Progression, Dose-Response Relationship, Drug, Female, Humans, Injections, Intravenous, Male, Middle Aged, Mitoxantrone, Multiple Sclerosis, Patient Compliance, Patient Dropouts, Recurrence, Retrospective Studies, Safety, Stroke Volume, United States, United States Food and Drug Administration, Young Adult|
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.
|Alternate Journal||Clin Neurol Neurosurg|