Short-term intensive cyclophosphamide treatment in progressive multiple sclerosis

Abstract

14 patients with chronic progressive multiple sclerosis, selected in a preliminary uncontrolled trial, were given a short course of intensive cyclophosphamide therapy, which was discontinued when the leukocyte count fell to 3000 cu.mm. 5 patients dropped out because of severe side effects. At 1 year follow-up were neurologically unchanged since admission to the trial; 4 remained stable at 2 years. The lack of clinical improvement, the high frequency of side effects and the proven oncogenicity of cyclophosphamide led us to discontinue the trial.

Treatment of multiple sclerosis with cyclophosphamide: critical review of clinical and immunologic effects

“…Reviewing these studies in light of what is now known about the underlying pathophysiology of MS our conclusion is that the 1983 NEJM report correctly identified cyclophosphamide as being effective in early, aggressive, inflammatory MS and incorrectly broadened the conclusion to progressive MS in general. The Canadian and Kaiser studies correctly demonstrated that in later stages of progressive MS or in MS that is not inflammatory or not rapidly progressive, cyclophosphamide is not effective but incorrectly concluded that cyclophosphamide had no efficacy in MS. Of note, type 2 errors can also be observed in smaller studies; a pilot study of mitoxantrone in progressive MS reported minimal efficacy and concluded that mitoxantrone was not worthy of further study in MS. 47 Recent studies utilizing pulse therapy and MRI Although there have been other reports of short 2-to 3-week courses of cyclophosphamide for the treatment of MS with both positive 48,49 and negative results, 50 most physicians currently use intermittent pulse therapy for the treatment of MS. Myers et al treated 14 patients with escalating monthly doses to as high as 2000 mg/m 2 , a regimen he found too toxic for long-term use. 69 Killian et al treated 14 relapsingremitting patients with monthly pulses of 750 mg/m 2 for 1 year in a pilot randomized, double-blind placebo-controlled trial that showed a positive trend ( p= 0.06) in 6 treated versus 8 placebo patients.…”