Cyclophosphamide and urinary bladder toxicity.

Abstract

Summary Single doses of cyclophosphamide can regularly induce bladder damage in rats and dogs. Changes develop rapidly and, within 24 hours, consist of ulceration of the mucosal epithelium, hemorrhage and edema in all bladder tissues, and necrosis in smooth muscle and small arteries. The epithelium and submucosa of the renal pelvis are similarly affected. Renal tubular necrosis is seen in a minority of the affected animals. During the first few hours after injection high concentrations of reactive material are excreted in the urine. Most of the alkylating activity is due neither to cyclophosphamide nor to bis( β -chloroethyl) amine. When reactive urine is introduced by catheter into dog bladders, it induces the typical changes seen after intravenous injection of cyclophosphamide. Bladder damage can be prevented by promoting an active diuresis during the first few hours after the injection of the agent. These observations show that bladder damage is probably a local response to contact by toxic bladder urine. They suggest means for preventing bladder complications in patients. They also provide evidence for the in vivo transformation of cyclophosphamide into circulating cytotoxic moieties.