Evaluation of local administration of ACNU in the treatment of malignant pleural effusion

Five patients with malignant pleural effusion were treated with intrapleural administration of ACNU. Three of 5 patients showed cytologically negative in the pleural fluid and the fluid was eliminated in two patients. In 5 patients, 200 mg of ACNU was injected into the pleural space and pharmacokinetic behavior was studied. The clearance curves of ACNU in pleural fluid were described by either one-compartment model or two-compartment model. The mean half life of slow phase was 0.75 hour. These results indicate that ACNU disappears rapidly from the pleural space after the intrapleural administration. The effect of ACNU on the pleura was studied histologically in rabbits. At a dose of 3mg per kg body weight, the mesothelial cells were swelling and small areas of cellular desquamation appeared over the pleural surface. With increase in dosage, these findings were more pronounced and in the submesothelial tissue there was edema as well as cellular infiltration. In rabbits given two injections with interval of one week, the pleura showed a stronger reaction than that produced by single injection.