Reduced gonadal toxicity after i.v. cyclophosphamide administration in patients with nonmalignant diseases

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.

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.

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.

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.