The carcinogenicity of ciclosporin.
Experimental data relevant for the evaluation of the carcinogenic potential of the immunosuppressant ciclosporin are reviewed: Firstly, the mode of action of ciclosporin at the level of lymphocyte gene transcription, secondly, the main adverse effects especially nephrotoxicity and thirdly, the results of the chronic bioassays. The experimental data are discussed together with the clinical evidence of increased incidence of tumors, especially lymphoproliferative disorders under ciclosporin immunosuppression. Conventional immunosuppression (azathioprine, anti-lymphocyte globulin, prednisone) also demonstrates comparable risks to develop tumors. Lympho-proliferative lesions regress after dose reduction or cessation of treatment. Furthermore, combinations of various immunosuppressants may result in a higher incidence of viral infection and malignancy. In summary, chemical immunosuppression carries the intrinsic risk of tumor growth. In the case of ciclosporin, which has no direct genotoxic effect, tumor promotion is probably dose-dependent. Thus, the risk may be reduced by low dosage and by avoiding combination therapies with additional immunosuppressants.
Ryffel
B
B
Institute of Toxicology, University of Zurich, Switzerland.
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D016572:Cyclosporine / Q000009:adverse effects* / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D009369:Neoplasms / Q000139:chemically induced*
D002273:Carcinogens; D007166:Immunosuppressive Agents; D016572:Cyclosporine