BACKGROUND: Cyclophosphamide has been used increasingly to treat patients with nonmalignant diseases like primary glomerulonephritis and systemic vasculitis. Thus long-term side effects like gonadal toxicity have become an important issue. Monthly i.v. cyclophosphamide pulse administration leads to a reduction in total dose of 60% compared to daily oral treatment which would be favorable for i.v. therapy. However, the risk of increased germinal damage due to higher peak levels had to be excluded. METHODS: Gonadal toxicity after different modes of cyclophosphamide administration was investigated in men with vasculitis or minimal change glomerulonephritis by measurement of FSH (follicle-stimulating hormone) plasma levels, as well as in Lewis rats by the investigation of testis histology and number of foetuses after mating with healthy female rats. RESULTS: FSH plasma levels after 3 months of treatment were significantly higher in men receiving daily oral cyclophosphamide (28.7 +/- 34 IU/l) compared to i.v. pulse administration (9.5 +/- 5.1 IU/l; p < 0.01) indicating a higher gonadal toxicity after oral treatment. In Lewis rats daily oral gavage led to a significantly reduced number of foetuses and changes in testis histology compared to pulse administration. CONCLUSION: As pulse administration of cyclophosphamide led to a significantly reduced gonadal toxicity compared to oral treatment this administration should be preferred, provided that an equal disease control and relapse rate is achieved.
BACKGROUND:Cyclophosphamide has been used increasingly to treat patients with nonmalignant diseases like primary glomerulonephritis and systemic vasculitis. Thus long-term side effects like gonadal toxicity have become an important issue. Monthly i.v. cyclophosphamide pulse administration leads to a reduction in total dose of 60% compared to daily oral treatment which would be favorable for i.v. therapy. However, the risk of increased germinal damage due to higher peak levels had to be excluded. METHODS:Gonadal toxicity after different modes of cyclophosphamide administration was investigated in men with vasculitis or minimal change glomerulonephritis by measurement of FSH (follicle-stimulating hormone) plasma levels, as well as in Lewis rats by the investigation of testis histology and number of foetuses after mating with healthy female rats. RESULTS: FSH plasma levels after 3 months of treatment were significantly higher in men receiving daily oral cyclophosphamide (28.7 +/- 34 IU/l) compared to i.v. pulse administration (9.5 +/- 5.1 IU/l; p < 0.01) indicating a higher gonadal toxicity after oral treatment. In Lewis rats daily oral gavage led to a significantly reduced number of foetuses and changes in testis histology compared to pulse administration. CONCLUSION: As pulse administration of cyclophosphamide led to a significantly reduced gonadal toxicity compared to oral treatment this administration should be preferred, provided that an equal disease control and relapse rate is achieved.
Authors: Julia Bontscho; Adrian Schreiber; Rudolf A Manz; Wolfgang Schneider; Friedrich C Luft; Ralph Kettritz Journal: J Am Soc Nephrol Date: 2011-01-13 Impact factor: 10.121