Cardiotoxicity and other adverse events associated with mitoxantrone treatment for MS. May 31, 2010.
Mitoxantrone is used for aggressive multiple sclerosis (MS) but concerns about safety, including cardiotoxicity and other laboratory measures prevail. Kingwell E., Koch M., Leung B., Isserow I., Geddes J., Rieckmann P., and Tremlett H. Neurology (in press).
Mitoxantrone is used for aggressive multiple sclerosis (MS)
but concerns about safety, including cardiotoxicity and other
laboratory measures prevail. Canadian researchers undertook to
evaluate the incidence and potential predictors of adverse events
associated with mitoxantrone at the MS Clinic, University of
British Columbia, Canada.
A retrospective review of patients treated with mitoxantrone by standard protocol (maximum cumulative dose=120mg/m2 ) was conducted. Left ventricular ejection fraction (LVEF) was measured with regular MUltiple-Gated Acquisition scans; blood cell counts and biochemical liver tests were performed prior to infusions. Generalized estimating equations were used to examine potential predictors of adverse events (graded according to the Common Toxicity Criteria, V.4) in patients with normal baseline and >one follow-up MUGA or laboratory assessment.
All 163 patients (58% women) treated with mitoxantrone from 1999-2007 were reviewed. Mean baseline age=41.9 years (SD:10.8), cumulative dose=59.7mg/m2 (SD:26.0) and median follow-up duration=14 months (maximum=6.5 years). By study end, 14% developed de novo cardiotoxicity (>grade two), as measured by decreased LVEF; 27 % neutropenia (>grade one); 15% anemia (>grade one) and 15% liver toxicity (>grade one). Possible predictors of adverse events included sex, age, disease duration and cumulative dose; only women exposed to a higher cumulative dose were at a greater risk of anemia (adjusted OR:1.26; 95%CI: 1.08-1.48 per 10mg/m2).
Conclusions: Based on cardiac and laboratory assessments, mitoxantrone was reasonably well tolerated. However, cardiotoxicity was evident following doses well below current maximum recommended levels. A dose-response effect was not apparent. Findings emphasize the importance of monitoring; the long-term effects of mitoxantrone in MS require investigation.
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