REDUCED GONADAL TOXICITY AFTER IV CYCLOPHOSPHAMIDE ADMINISTRATION IN PATIENTS WITH NONMALIGNANT DISEASES

Background: Cyclophosphamide has been used increasingly to treat patie nts with nonmalignant diseases like primary glomerulonephritis and sys temic vasculitis. Thus long-term side effects like gonadal toxicity ha ve become an important issue. Monthly i.v. cyclophosphamide pulse admi nistration leads to a reduction in total dose of 60% compared to daily oral treatment which would be favorable for i.v. therapy. However, th e risk of increased germinal damage due to higher peak levels had to b e excluded. Methods: Gonadal toxicity after different modes of cycloph osphamide administration was investigated in men with vasculitis or mi nimal change glomerulonephritis by measurement of FSH (follicle-stimul ating hormone) plasma levels, as well as in Lewis rats by the investig ation of testis histology and number of foetuses after mating with hea lthy female rats. Results: FSH plasma levels after 3 months of treatme nt were significantly higher in men receiving daily oral cyclophospham ide (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 tre atment. In Lewis rats, daily oral gavage led to a significantly reduce d number of foetuses and changes in testis histology compared to pulse administration. Conclusion: As pulse administration of cyclophosphami de led to a significantly reduced gonadal toxicity compared to oral tr eatment this administration should be preferred, provided that an equa l disease control and relapse rate is achieved.