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Cyclophosphamide

This is a rather toxic anti-cancer drug. It is used, particularly in combination with other chemotherapy agents, for such diseases as lymphomas, multiple myeloma, breast, lung, cervix and ovary cancer, and several childhood cancers. It has the advantage of being able to be given by mouth rather than injection only, unlike most of the other anti-cancer agents. In MS, cyclophosphamide has mostly been used for the chronic progressive form. Several RCTs have not shown any benefit for either cyclophosphamide alone compared with placebo,1 or different combinations of cyclophosphamide, steroids and other techniques.2 A later study from Harvard Medical School, however, showed that people who had cyclophosphamide and steroids to induce immunosuppression, and then had booster doses of cyclophosphamide every other month for two years, had slower progression of disease than those without the boosters.3 This was a large RCT of 256 people with MS. The group who had the booster injections had slower progression of disability at 24 and 30 months, but the effect was confined to those patients under forty years of age. For this group of patients, the effect was very significant.
Another study from Boston in 2005 looked at people who were not responding well to interferon therapy, that is their disease was still quite active.4 They randomized patients to receive either monthly cyclophosphamide and steroids or monthly steroids alone in addition to their interferon therapy. The cyclophosphamide group did considerably better, presenting another treatment option for people not responding well to interferons alone. An Italian study monitored 10 patients with rapidly progressive MS who were given monthly doses of cyclophosphamide in combination with interferon beta, and then maintained on interferon beta alone.5 They were quite stable clinically and on MRI at 36 months. One intriguing report from Brazil noted that a 48 year old woman who had accidentally been given a very high single dose of cyclophosphamide three years after diagnosis, had not had any disease activity of any sort seven years later.6

Unfortunately cyclophosphamide has major side-effects, both short and long term. It causes hair to fall out, nausea and vomiting, ulceration of the mouth and other mucous membranes, dizziness, and increased skin pigmentation. More serious effects are bladder irritation with blood in the urine, and bone marrow suppression, with increased susceptibility to infections. In the longer term, it can cause a variety of cancers in its own right. These side-effects limit its usefulness for people with MS.
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  1. Likosky WH, Fireman B, Elmore R, et al. Intense immunosuppression in chronic progressive multiple sclerosis: the Kaiser study. J Neurol Neurosurg Psychiatry 1991; 54:1055-1060
  2. The Canadian Cooperative Multiple Sclerosis Study Group. The Canadian Cooperative trial of cyclophosphamide and plasma exchange in progressive multiple sclerosis. Lancet 1991; 337:441-446
  3. Weiner HL, Mackin GA, Orav EJ, et al. Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the Northeast Cooperative Multiple Sclerosis Treatment Group. Neurology 1993; 43:910-918
  4. Smith DR, Weinstock-Guttman B, Cohen JA, et al. A randomized blinded trial of combination therapy with cyclophosphamide in patients-with active multiple sclerosis on interferon beta. Mult Scler 2005; 11:573-582
  5. Patti F, Reggio E, Palermo F, et al. Stabilization of rapidly worsening multiple sclerosis for 36 months in patients treated with interferon beta plus cyclophosphamide followed by interferon beta. J Neurol 2004; 251:1502-1506
  6. Bittencourt PR, Gomes-da-Silva MM. Multiple sclerosis: long-term remission after a high dose of cyclophosphamide. Acta Neurol Scand 2005; 111:195-198