Abstract
Pulmonary vasculitis is a potentially lethal autoimmune disease characterized by granulomatous inflammation of respiratory tract, necrotizing vasculitis affecting small-to medium-size vessels and antineutrophil cytoplasmic antibodies elevation. Typical therapy involves high-dose glucocorticosteroids combined with cyclophosphamide in a dose 1–2 mg/kg/per day. A high relapse rate in pulmonary vasculitis means prolonged courses of cyclophosphamide in some patients. Carcinogenic effects of cyclophosphamide, especially its toxic metabolite acrolein that is excreted into the urine, are responsible for the development of acute myeloid leukemia (AML) and bladder cancer. These and other malignancies are cyclophosphamide dose-depended. The aim of the present study was to assess the incidence of cancer in patients with pulmonary vasculitis in comparison with the incidence of cancer in the general population. Analyses were done according to the cumulative dose of cyclophosphamide, subdivided into low (≤35 g) and high (>35 g). During the observation period 15 cancers occurred. A significantly increased standardized incidence ratio (SIR) was observed for non-melanoma skin cancers (SIR 5.2; 95 % Cl 2.3–8.7), AML (SIR 4.3; 95 % Cl 2.1–11.2), and bladder cancer (SIR 3.4; 95 % Cl 1.6–5.2). Induction remission treatment and relapse treatment with cyclophosphamide involves a substantial risk of late appearing malignances in patients with pulmonary vasculitis. Monitoring and prophylactic management in pulmonary vasculitis after cessation of cyclophosphamide therapy is crucial.
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References
Bernatsky, S., Ramsey-Goldman, R., & Clarke, A. E. (2008). Malignancies and cyclophosphamide exposure in Wegener’s granulomatosis. Journal of Rheumatology, 35(1), 11–13.
Colvin, O. M. (1999). An overview of cyclophosphamide’s development and clinical application. Current Pharmaceutical Design, 5(8), 555–560.
Faurschou, M., Sorensen, I. J., Mellemkjaer, L., Loft, A. G., Thomsen, B. S., Tvede, N., & Baslund, B. (2008). Malignancies in Wegener’s granulomatosis: Incidence and relation to cyclophosphamide therapy in a cohort of 293 patients. Journal of Rheumatology, 35(1), 100–105.
Faurschou, M., Mellemkjaer, L., Sorensen, I. J., Thomsen, B. S., Dreyer, L., & Baslund, B. (2009). Cancer preceding Wegener’s granulomatosis: A case–control study. Rheumatology (Oxford, England), 48(4), 421–424.
Heijl, C., Harper, L., Flossmann, O., Stücker, I., Scott, D. G., Watts, R. A., Höglund, P., Westman, K., Mahr, A., & European Vasculitis Study Group (EUVAS). (2011). Incidence of malignancy in patients treated for antineutrophil cytoplasm antibody-associated vasculitis: Follow-up data from European Vasculitis Study Group clinical trials. Annals of the Rheumatic Diseases, 70(8), 1415–1421.
Hoff, M., & Rødevand, E. (2005). Development of multiple malignancies after immunosuppression in a patient with Wegener’s granulomatosis. Rheumatology International, 25(3), 238–240.
International Classification of Disease. http://www.euro.who.int/hfadb. Accessed 30 Oct 2012.
Knight, A., Ascling, J., & Ekbom, A. (2002). Cancer incidence in population-based cohort of patients with Wegener’s granulomatosis. International Journal of Cancer, 100, 82–85.
Le Guenno, G., Mahr, A., Pagnoux, C., Dhote, R., Guillevin, L., & French Vasculitis Study Group. (2011). Incidence and predictors of urotoxic adverse events in cyclophosphamide-treated patients with systemic necrotizing vasculitides. Arthritis and Rheumatism, 63(5), 1435–1445.
Molloy, E. S., & Langford, C. A. (2008). Balancing efficacy and cancer risk of cyclophosphamide for patients with Wegener’s granulomatosis. Nature Clinical Practice Rheumatology, 4(7), 340–341.
Pankhurst, T., Savage, C. O., Gordon, C., & Harper, L. (2004). Malignancy is increased in ANCA-associated vasculitis. Rheumatology (Oxford, England), 43(12), 1532–1535.
Polish National Cancer Registry. http://www.euro.who.int/hfadb. Accessed 25 Oct 2012.
Sharma, P., Sharma, S., Baltaro, R., & Hurley, J. (2011). Systemic vasculitis. American Family Physician, 85(3), 556–565.
Silva, F., Seo, P., Schroeder, D. R., Stone, J. H., Merkel, P. A., Hoffman, G. S., Spiera, R., Sebastian, J. K., Davis, J. C., Jr., St Clair, E. W., Allen, N. B., McCune, W. J., Ytterberg, S. R., Specks, U., & Wegener’s Granulomatosis Etanercept Trial Research Group. (2011). Solid malignancies among etanercept-treated patients with granulomatosis with polyangiitis (Wegener’s): Long-term followup of a multicenter longitudinal cohort. Arthritis and Rheumatism, 63(8), 2495–2503.
Stone, J. H., Holbrook, J. T., Marriott, M. A., Tibbs, A. K., Sejismundo, L. P., Min, Y. I., Specks, U., Merkel, P. A., Spiera, R., Davis, J. C., St Clair, E. W., McCune, W. J., Ytterberg, S. R., Allen, N. B., Hoffman, G. S., & Wegener’s Granulomatosis Etanercept Trial Research Group. (2006). Solid malignancies among patients in the Wegener’s Granulomatosis Etanercept Trial. Arthritis and Rheumatism, 54(5), 1608–1618.
Takala, J. H., Kautiainen, H., & Leirisalo-Repo, M. (2010). Survival of patients with Wegener’s granulomatosis diagnosed in Finland in 1981–2000. Scandinavian Journal of Rheumatology, 39(1), 71–76.
Talar-Williams, C., Hijazi, Y. M., & Walther, M. M. (1996). Cyclophosphamide-inducted cystitis and bladder cancer in patients with Wegener’s granulomatosis. Annals of Internal Medicine, 124, 477–484.
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Zycinska, K., Kostrzewa-Janicka, J., Nitsch-Osuch, A., Wardyn, K. (2013). Cancer Incidence in Pulmonary Vasculitis. In: Pokorski, M. (eds) Neurobiology of Respiration. Advances in Experimental Medicine and Biology, vol 788. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6627-3_47
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