Assessment of potential cardiotoxic side effects of mitoxantrone in patients with multiple sclerosis

Previous studies showed that mitoxantrone can reduce disability
progression in patients with multiple sclerosis (MS). There is,
however, concern that it may cause irreversible cardiomyopathy with
reduced left ventricular (LV) ejection fraction (EF) and congestive
heart failure. The aim of this prospective study was to investigate
cardiac side effects of mitoxantrone by repetitive cardiac
monitoring in MS patients. The treatment protocol called for ten
courses of a combined mitoxantrone (10 mg/m(2) body surface) and
methylprednisolone therapy. Before each course, a transthoracic
echocardiogram was performed to determine the LV end-diastolic
diameter, the end-systolic diameter and the fractional shortening;
the LV-EF was calculated. Seventy-three patients participated (32
males; age 48 +/- 12 years, range 20-75 years; 25 with primary
progressive, 47 with secondary progressive and 1 with
relapsing-remitting MS) who received at least four courses of
mitoxantrone. Three of the 73 patients were excluded during the
study (2 patients discontinued therapy; 1 patient with a previous
history of ischemic heart disease developed atrial fibrillation
after the second course of mitoxantrone). The mean cumulative dose
of mitoxantrone was 114.0 +/- 33.8 mg. The mean follow-up time was
23.4 months (range 10-57 months). So far, there has been no
significant change in any of the determined parameters
(end-diastolic diameter, end-systolic diameter, fractional
shortening, EF) over time during all follow-up investigations.
Mitoxantrone did not cause signs of congestive heart failure in any
of the patients. Further cardiac monitoring is, however, needed to
determine the safety of mitoxantrone after longer follow-up times
and at higher cumulative doses. Copyright (C) 2005 S. Karger AG,
Basel.