Long-Term Follow-up Data of Mitoxantrone (Novatrone) in MS Show Good Safety and Tolerability
Five-year cardiac and haematological data from a large cohort of multiple sclerosis (MS) patients show that mitoxantrone is generally well tolerated and safe. The results on mitoxantrone, which is routinely used in the treatment of leukaemia, malignant melanoma, and breast cancer, were presented here during the 58th annual meeting of the American Association of Neurology (AAN).
Lead researcher
Emmanuelle Le Page,
neurologist,
Centre hospitalier
universitaire de Rennes,
Bretagne, France, and
colleagues conducted their 5-year follow-up study in 12 centers in France.
Mitoxantrone was administered in;
307 patients with relapsing-remitting MS,
352 with secondary progressive MS, and
143 with primary progressive MS.
At 5 years, 776 were assessed clinically at 5 years, for a total of 5361 patient years. The remaining 26 patients were lost to follow-up.
Mitoxantrone was administered monthly for 6 months in 695, and every 3 months in 107 patients. The mean dose was 78 mg/m2, and 18.5% of mitoxantrone patients received a cumulative dose of more than 100 mg/m2.
"We observed a decrease in the left ventricular ejection fraction (LVEF) of <50% in 40 patients," Dr. Le Page explained. "One patient suffered congestive heart failure, a 54 year-old woman. Two patients developed acute neoplastic leukemia; the first died, and the second was in stable condition, in hematologic remission, at the time of reporting."
55 patients died on study,
33 of which were MS-related;
17 were deemed not to be mitoxantrone or MS related.
1 death was mitoxantrone related,
the first case of therapy related leukaemia, which occurred 27 months following the initiation of treatment," Dr. Le Page said.
The researchers also assessed the effects of mitoxantrone on menses in 317 women aged 45 years or less. The data revealed that
27.1% developed intermittent amenorrhea, and
17.3% persistent amenorrhoea.
(Amenorrhoea – the abnormal absence or suppression of menstruation)
The study found a
4.5% risk of amenorrhoea for women who are treated when they are between 25 and 29 years old, a
10% risk in women between 30 and 34 years, and a
21% risk when treated between 35 and 39 years of age.
"To summarize, when women were treated prior to age 35 years, the risk was 5.4%, and it was 30.7% when they were treated at 35 years of age.
In the population studied, the risk of developing congestive heart failure at 5 years was 0.5%, the risk for transient symptomatic or persistent asymptomatic LVEF was 3.3% and 1.3%, respectively. The risk for acute neoplastic leukaemia was 0.25%, and according to Dr. Le Page, 0.1% of deaths were related to mitoxantrone.
Dr. Le Page and colleagues concluded that the mitoxantrone dose of 78 mg/m2 was generally well tolerated as administered in this study.
"This study pointed out the importance of monitoring cardiac and haematologic tolerance during and after treatment by echocardiography every year, and white blood cell counts every 3 months for 5 years following treatment [with mitoxantrone]," she said.
Safety Profile of Mitoxantrone in a French Cohort of 802 Multiple Sclerosis Patients: a 5-Year Follow-Up Study.