title: Assessment of potential cardiotoxic side effects of mitoxantrone in patients with multiple sclerosis.
abstract: 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.
authors.affiliation: Department of Neurology, University of Munich, Munich, Germany. vzingler@nro.med.uni-muenchen.de
authors.forename: Vera Carina
authors.initials: VC
authors.lastname: Zingler
authors.forename: Michael
authors.initials: M
authors.lastname: Nabauer
authors.forename: Klaus
authors.initials: K
authors.lastname: Jahn
authors.forename: Ariane
authors.initials: A
authors.lastname: Gross
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hohlfeld
authors.forename: Thomas
authors.initials: T
authors.lastname: Brandt
authors.forename: Michael
authors.initials: M
authors.lastname: Strupp
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004452:Echocardiography; D005260:Female; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D008942:Mitoxantrone / Q000009:adverse effects*; D009103:Multiple Sclerosis / Q000188:drug therapy*
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D008942:Mitoxantrone; D008775:Methylprednisolone