Clinical pharmacology and toxicology of cyclophosphamide: emphasis on use in rheumatic diseases

Kovarsky, Joel

doi:10.1016/0049-0172(83)90016-1

Cited by 72 publications

(20 citation statements)

References 152 publications

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“…CTX, an alkylating agent used to treat many malignant and autoimmune diseases [19,20], was found to induce a pronounced immune deviation, favoring Th2-type responses specific to autoantigens, in MS patients. Indeed, CTX-treated patients showed increased eosinophil counts that were positively and significantly correlated with an upregulation of interleukin-4 (IL-4) production by peripheral blood mononuclear cells (PBMC) [21].…”

Section: Discussionmentioning

confidence: 99%

Cyclophosphamide is effective in stabilizing rapidly deteriorating secondary progressive multiple sclerosis

Perini

Gallo

2003

J Neurol

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The safety and efficacy of pulse cyclophosphamide (CTX) therapy was investigated in patients with very active secondary progressive multiple sclerosis, characterized by frequent relapses and rapid disability progression. For this purpose the clinical and MRI effects were assessed. Sixteen patients, 11 female and 5 male, were experiencing rapidly deteriorating disease, characterized by frequent and severe relapses as well as rapid progression (defined by an increase of more than 1 EDSS point in a period of 1 year). Mean relapse rate in the two years preceding CTX therapy was 3.0 +/-1.4. Mean EDSS was 4.0+/-1.4 one year before therapy and 5.6+/-1.0 at study entry. Treatment consisted in administration of high dose intravenous CTX every four weeks for one year and then every eight weeks for an additional twelve months. CTX dose was tailored to the patient's white blood cell response, and ranged from 800 to 1,200 mg/m(2) body surface. MRI was performed before therapy and then at 12 (Y1) and 24 (Y2) months. Eight patients with similar clinical features constituted a control group. CTX therapy was safe and well tolerated, and no severe side effects were observed. The EDSS decreased to 4.3+/-1.6 at Y1 (Y0 vs.Y1: p< 0.001) and to 4.1+/-1.6 at Y2 (Y0 vs.Y2: p< 0.001). Only four patients experienced relapses during the first year of therapy, while no relapses were observed during the second year of therapy. The mean relapse rate during therapy was 0.25 +/-0.45 (p< 0.0001). No increase in T2 lesion load was observed over the two years. A significant clinical and MRI deterioration was observed in the control group. Therapy with pulse CTX was able to stop disease activity and progression in patients with rapidly evolving secondary-progressive MS.

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Section: Discussionmentioning

confidence: 99%

Cyclophosphamide is effective in stabilizing rapidly deteriorating secondary progressive multiple sclerosis

Perini

Gallo

2003

J Neurol

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“…This working concentration translated to 7.5 mM cyclophosphamide. Cyclophosphamide, however, is considered inactive in all in vitro experiments, because it requires liver hepatocyte p-450 system to generate active cytotoxic metabolites (21). Therefore, in all our in vitro experiments, we used 4-HC, which spontaneously converts to 4-hydroxycyclophosphamide in aqueous solution.…”

Section: Resultsmentioning

confidence: 99%

Thrombospondin-1 Associated with Tumor Microenvironment Contributes to Low-Dose Cyclophosphamide-Mediated Endothelial Cell Apoptosis and Tumor Growth Suppression

et al. 2004

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“…CPA, alkylating agent which inhibit synthesis of DNA, induces pancytopenia and bone-marrow suppression by cytostatic activity (Kovarsky, 1983). In the present study, oral administration of CPA at 2 mg/kg for a consecutive 28 days significantly decreased primary and secondary KLH responses.…”

Section: Discussionmentioning

confidence: 54%

Evaluation of canine T-cell dependent antibody response to the primary and secondary immunization with keyhole limpet hemocyanin

et al. 2013

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-T-cell dependent antibody response (TDAR) incorporating both primary and secondary responses to keyhole limpet hemocyanin (KLH) in canine models have not yet been fully understood. To develop a practical dog TDAR model, we characterized primary and secondary antibody responses by intravenous or intramuscular immunization of KLH twice at intervals of 8 days during a 28-day course of study. Primary immunization with KLH by both routes induced a maximum IgM response on 6 to 8 days after the treatment, whereas the IgG response started 6 to 8 days after the treatment with relatively low levels. Remarkable increases in anti-KLH IgG levels (about 10-times compared with the primary response) were produced 5 to 7 days after the secondary KLH immunization by both routes. These results indicate that IgM-predominant and IgG-predominant responses were respectively induced by the primary and secondary immunization. Furthermore, the intravenous route showed higher baseline titers of primary and secondary anti-KLH IgM responses, suggesting that intravenous immunization of KLH might be a more suitable method for immunotoxicity evaluation. No remarkable inter-individual variability was noted in our canine models. Treatment with cyclophosphamide at 2 mg/kg/day for a consecutive 28 days significantly suppressed primary and secondary anti-KLH IgM and IgG responses induced by KLH injection on Days 15 and 23 of CPA treatment. These results demonstrate that these experimental designs could provide valuable information about the influence on both the primary and secondary humoral immune responses in dogs when exposed to potential immunomodulatory drugs.

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Clinical pharmacology and toxicology of cyclophosphamide: emphasis on use in rheumatic diseases

Cited by 72 publications

References 152 publications

Cyclophosphamide is effective in stabilizing rapidly deteriorating secondary progressive multiple sclerosis

Cyclophosphamide is effective in stabilizing rapidly deteriorating secondary progressive multiple sclerosis

Thrombospondin-1 Associated with Tumor Microenvironment Contributes to Low-Dose Cyclophosphamide-Mediated Endothelial Cell Apoptosis and Tumor Growth Suppression

Evaluation of canine T-cell dependent antibody response to the primary and secondary immunization with keyhole limpet hemocyanin

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