Assessment of potential cardiotoxic side effects of mitoxantrone in patients with multiple sclerosis – an interim analysis after five years

Introduction: Several studies have shown that mitoxantrone (mitox) may have beneficial effect on the course of disease in patients with multiple sclerosis (MS). There is, however, concern that its potentially cumulative cardiotoxic side effects may cause cardiomyopathy, reduced left ventricular (LV) ejection fraction (EF), and irreversible congestive heart failure (CHF). Therefore the aim of this study was to investigate cardiac side-effects by repetitive monitoring.

Methods: In this prospective study 73 patients with a rapidly deteriorating primary (PP) or secondary (SP) progressive MS or a severe relapsing-remitting (RR) form were included. The treatment protocol called for ten courses of mitox (10mg/sqm body surface). Before each course a transthoracic echocardiogram was performed to determine the LV-enddiastolic diameter (EDD) and the endsystolic diameter (ESD); the LV-EF was calculated.

Results: 73 patients (41 females, 32 males; age 48±12 years, range 20–75 years) were enrolled in the study. 25 patients had a PP-, 47 patients an SP-, and 1 patient an RR-form of MS. Three of the 73 patients were excluded (two patients discontinued therapy; one patient with a previous history of ischemic heart disease developed atrial fibrillation after the second treatment with mitox). The remaining 70 patients completed at least four courses of therapy. The mean cumulative dose of mitox was 114.0±33.8mg. The initial mean-EDD was 47.5±5.7mm, mean-ESD 28.2±4.7mm, and the mean-EF 64.7±5.7%. On follow-up investigations after four courses the mean-EDD was 46.8±4.5mm, mean-ESD 27.9±3.7mm, mean-EF 64.3±5.9%; and after eight courses the mean-EDD was 45.5±3.3mm, mean-ESD 27.1±4.6mm, mean-EF 64.0±8.1%. Thus, up to now there was no significant change of all parameters over time. None of the patients had any regional wall motion abnormalities or experienced CHF.

Conclusion: Mitox (10mg/sqm) did not cause a reduction of LV-EF or signs of CHF in any of the investigated patients. Further long-term cardiac monitoring is, however, needed to determine the safety of mitox after application of higher cumulative doses.