Sept 23, 2002
There is a small but significant risk of developing congestive heart failure (CHF) among patients with multiple sclerosis (MS) who are receiving mitoxantrone (Novantrone), according to a report in the September 24th issue of Neurology.
"We undertook this study because the risk of cardiac toxicity after single-agent mitoxantrone therapy for MS has not been rigorously examined," Dr. Donald E. Goodkin, from Amgen Corp., and colleagues reported.
Dr. Goodkin and colleagues studied the data from three clinical trials, which included 1,378 patients with MS. The researchers reviewed the patients' records for left ventricular ejection fraction (LVEF) results and signs and symptoms of cardiac dysfunction.
In the trials, cumulative doses of mitoxantrone ranged from 2 milligrams per meter squared to 183 milligrams per meter squared, with 141 patients receiving more than 100 milligrams per meter squared, the investigators note.
During a median follow-up of 29 months, two patients developed CHF after starting mitoxantrone therapy.
Baseline LVEFs were greater than 50% for all of the 779 patients who had LVEFs measured at baseline and completed all follow-up measurements. After starting mitoxantrone, 17 (2.18%) of these patients developed asymptomatic LVEFs of less than 50%, Dr. Goodkin's team found.
Although the frequency of this change in LVEF was not associated with duration of therapy, age or gender, it trended higher in patients receiving cumulative doses of mitoxantrone of 100 milligrams per meter squared or more (5.0%) than in patients receiving less than 100 milligrams per meter squared (1.8%; p = 0.06), the researchers note.
"Guidance for the use of mitoxantrone in patients with MS is contained in the package insert for Novantrone," Dr. Goodkin and colleagues conclude. "This documentation indicates tests of LVEF should be obtained prior to initiating therapy, whenever there are symptoms of CHF, and prior to every infusion after reaching a cumulative dose of 100 milligrams per meter squared."
"Further, treatment should not ordinarily be initiated or continued in patients with LVEF of less than 50% or CHF or patients with clinically significant reduction in LVEF," they add.
The study was supported by a grant from Immunex Corp., U.S. marketer of mitoxantrone, now doing business as Amgen Corp., in Seattle, WA.
© 2002 Reuters Ltd