Intravenous mitoxantrone and cyclophosphamide as second-line therapy in multiple sclerosis: an open-label comparative study of efficacy and safety.
The study's aim was to compare the efficacy and safety of intravenous cyclophosphamide (CTX) and mitoxantrone (MITO) as second-line therapy in a clinical sample of active relapsing-remitting (RR) or secondary-progressive (SP) multiple sclerosis subjects. MITO was administered at a dosage of 8 mg/m(2) monthly for 3 months, then every 3 months, until a dosage of 120 mg/m(2) was reached. CTX was administered at a dosage of 700 mg/m(2) monthly for 12 months, then bimonthly for another 24 months. We used the Kaplan-Meier curves to assess time to the first relapse in RR and SP patients with relapses, and time to progression on the Expanded Disability Status Scale (EDSS) in all the patients. MRI was assessed at baseline and after 12 months. Moreover, side effects were recorded. Seventy-five patients received MITO (31 RR, 44 SP) and 78 CTX (15 RR, 63 SP). The two groups differ only in terms of a significantly higher proportion of RR patients in the MITO group. After a mean follow-up of 3.6 years there was no significant difference in terms of time to the first relapse (MITO 2.6 years, CTX 2.5 years; p=0.50), whereas time to disease progression was slightly shorter in MITO than in CTX group (MITO 3.8 years, CTX 3.6 years; p=0.04). After 12 months of treatment, active MRI scans were reduced by 69% in MITO and 63% in CTX patients (p=0.10). Discontinuation due to side effects was more frequent in CTX patients. However, the overall tolerability profile was acceptable in both groups.
Zipoli
Valentina
V
Department of Neurology, University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
Portaccio
Emilio
E
Hakiki
Bahia
B
Siracusa
Gianfranco
G
Sorbi
Sandro
S
Amato
Maria Pia
MP
D000328:Adult; D000477:Alkylating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001772:Blood Cell Count; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D008942:Mitoxantrone / Q000009:adverse effects / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy*; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy; D011788:Quality of Life; D012044:Regression Analysis; D016896:Treatment Outcome
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D008942:Mitoxantrone