Local and systemic effects of repeated intraperitoneal epirubicin treatment

The local toxicity, general morbidity and mortality of repeated intraperitoneal administration of epirubicin (0.5 mg/kg in 100 ml isotonic saline) was investigated using a rat model. This dose is equivalent to that which would be used in the human. After six perfusions, the incidence of peritoneal inflammation was similar in the epirubicin group and saline controls. The vesicant properties of the drug were reflected in a significantly higher incidence of peritoneal fibrosis (P = 0.0015) but adhesions were more common in the controls (29%) than in the epirubicin perfused animals (4%). Animals from both groups showed inflammatory collections within the liver. There were no chronic hepatic lesions such as fibrosis/cirrhosis. This may be owing to portal bacteraemia caused by repeated cannulation of the peritoneal cavity. Evidence of microabscess formation in the hepatic parenchyma was observed in both animals. No histologically demonstrable toxicity was observed in the heart or gastrointestinal tract of the animals included in this study. The mortality of the epirubicin treated rats (2/146 perfusions) was similar to that of the saline controls (2/84 perfusions). These findings indicate that repeated intraperitoneal perfusion with epirubicin is not associated with significant toxicity. This anthracycline is therefore suitable for prolonged cyclical intraperitoneal chemotherapy.