Controlled Pilot Trial of Monthly Intravenous Cyclophosphamide in Multiple Sclerosis

Killian, James M.; Bressler, Robert B.; Armstrong, Richard M.; Huston, David P.

doi:10.1001/archneur.1988.00520250033014

Cited by 46 publications

(20 citation statements)

References 20 publications

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“…A clinical experience with CY in MS for the last 30 years has confirmed its potent anti-inflammatory activity as reflected by its efficacy on relapses [59] and on active, Gd-enhancing brain lesions [60]. The response to CY administration is clearly linked to the stage of the disease.…”

Section: Cyclophosphamidementioning

confidence: 99%

Compared benefit of approved and experimental immunosuppressive therapeutic approaches in multiple sclerosis

Gonsette¹

2007

Expert Opinion on Pharmacotherapy

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An important amount has been learnt about the mechanisms of action, efficacy and long-term toxicities of mitoxantrone. Importantly, recent observations strongly suggest that early administration of potent immunosuppressants (mitoxantrone and alemtuzumab) is definitely more effective than approved immunomodulators to delay or even reverse disability progression. Given the cardiotoxicity of mitoxantrone, restricting exposure to the drug to 2 or 3 years, the benefits and risks of immunosuppressants previously used as off-label treatments (cyclophosphamide and cladribine) have been revisited, and the potential efficacy in multiple sclerosis of recent immunosuppressants used in other autoimmune diseases, organ transplantation and cancer therapy has received increasing attention. Those immunosuppressants comprise monoclonal antibodies targeting B cells, lymphocytes and monocytes, IL-2 receptor and alpha4 integrin, as well as new molecules (pixantrone and isoxazole derivatives) and a new generation of immunosuppressants (fingolimod), which modulate lymphocyte re-circulation. This review addresses the most recent data concerning the efficacy and safety of mitoxantrone and of new experimental therapies that are presently in progress.

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Section: Cyclophosphamidementioning

confidence: 99%

Compared benefit of approved and experimental immunosuppressive therapeutic approaches in multiple sclerosis

Gonsette¹

2007

Expert Opinion on Pharmacotherapy

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“…Multiple sclerosis (MS) treatment, for instance, uses immunosuppressive agents. A clinical experience with CY in MS has confirmed its potent antiinflammatory activity as reflected by its efficacy against relapses [17] and active brain lesions [18]. The response to CY administration is clearly linked to the stage of the disease.…”

Section: Discussionmentioning

confidence: 92%

Does Cyclophosphamide Play a Protective Role Against Neuronal Loss in Chronic T. cruzi Infection?

et al. 2008

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In this study, we verified the possible role of cyclophosphamide (CY) in protecting or not against neuronal losses in young and aged male Calomys callosus chronically infected with the MORC-1 strain of Trypanosoma cruzi through numerical quantification of neurons from the myenteric plexus of the colon and quantification of nitric-oxide concentration (NO) during the acute and chronic phase of infection. For this purpose, groups of young C. callosus were infected with the MORC-1 strain of T. cruzi. A group of infected animals received i.p. 0.2 mg/ml genuxal dissolved in distilled water treatment with CY. NO concentration in aged animals displayed reduced levels when compared to those found in young animals. No significant alterations in the number of neurons were observed in young animals, but for aged ones, a protective role of CY in reducing neuron loss was noted, in addition to enhancing the neuronal volume, area, and perimeter. These results suggest that CY administration, depending on the dose and time span, can act as a protective agent against neuronal losses.

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“…The clinical efficacy of CFX in progressive MS is still debated. The poor tolerability of induction phase suggests the need to investigate other safer schedules [13,14]. The optimal treatment schedule must be better investigated, in order to obtain clinical benefits with limited side effects.…”

Section: Discussionmentioning

confidence: 99%

“…A more frequent stabilization of the disease has been obtained with a maintenance program with boosters every other month, after an induction phase [8,9]. In order to decrease the risk of urotoxicity and immunodepression associated with these protocols [8,9], alternative schedules with monthly boluses, already used for treatment of autoimmune diseases [10][11][12], have been proposed [13,14]. To evaluate the safety and clinical efficacy of CFX in progressive MS, we compared three different schedules: induction followed by bimonthly boosters for one year; bimonthly boosters for one year without previous induction; and monthly boosters for one year.…”

Section: Introductionmentioning

confidence: 99%

Cyclophosphamide in chronic progressive multiple sclerosis: a comparative study

Mantia¹,

Eoli²,

Salmaggi³

et al. 1998

Ital J Neuro Sci

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No effective treatment is presently available for progressive multiple sclerosis (MS). Cyclophosphamide (CFX), a cytotoxic immunosuppressive drug widely used in systemic dysimmune diseases, has been proposed for the treatment of multiple sclerosis with different schedules and controversial results. To evaluate the safety and clinical efficacy of CFX, we compared three different treatment schedules in patients with progressive MS: induction followed by bimonthly boosters for one year (17 patients); bimonthly boosters for one year without previous induction (15 patients); and monthly boosters for one year (21 patients). Survival analysis showed that the percentage of stable patients was significantly higher in the first and third treatment schedule groups. Myelotoxicity occurred in patients treated with induction and boosters (Group A). A high incidence of broncopneumonia was observed in patients undergoing the second treatment schedule (Group B). No major effects were observed in patients treated with monthly boosters (Group C). Response to treatment was limited to secondary progressive form. This study suggests that monthly treatment with CFX might be safely administered in progressive MS patients; its clinical efficacy must be confirmed by an appropriately designed clinical trial.

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Controlled Pilot Trial of Monthly Intravenous Cyclophosphamide in Multiple Sclerosis

Cited by 46 publications

References 20 publications

Compared benefit of approved and experimental immunosuppressive therapeutic approaches in multiple sclerosis

Compared benefit of approved and experimental immunosuppressive therapeutic approaches in multiple sclerosis

Does Cyclophosphamide Play a Protective Role Against Neuronal Loss in Chronic T. cruzi Infection?

Cyclophosphamide in chronic progressive multiple sclerosis: a comparative study

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