COMPARISON OF NITROGEN-MUSTARD, CYTARABINE AND DACARBAZINE AS PLEURALSCLEROSING AGENTS IN RABBITS

We have previously shown that the intrapleural injection of mitozantro ne but not bleomycin resulted in pleural fibrosis. Mechlorethamine hyd rochloride (nitrogen mustard) was used extensively in the past to cont rol malignant effusions, with relatively good success. The objective o f this study was to determine if the intrapleural injection of nitroge n mustard would produce pleural sclerosis in our experimental model in rabbits. We therefore evaluated sclerosing capabilities of nitrogen m ustard as well as those of cytarabine and dacarbazine. Nitrogen mustar d (0.4 and 0.8 mg . kg(-1)), cytarabine (3, 6 and 20 mg . kg(-1)) and dacarbazine (4, 8 and 20 mg . kg(-1)), were instilled intrapleurally i nto anaesthetized rabbits. Twenty eight days after the instillation, t he animals were killed, and the pleural spaces were assessed grossly f or evidence of pleurodesis and microscopically for evidence of fibrosi s and inflammation. The intrapleural injection of 0.8 mg . kg(-1) nitr ogen mustard was effective in creating pleural fibrosis, either grossl y or microscopically. The mean degree (scale 0-4) of gross pleurodesis in the rabbits that received 0.8 mg . kg(-1) nitrogen mustard was 3.2 +/-1.0 and the mean degree of microscopic pleural fibrosis was 3.5+/-0 .8. The intrapleural injection of 0.4 mg . kg(-1) nitrogen mustard and the different doses of cytarabine (3, 6 and 20 mg . kg(-1)) and dacar bazine (4, 8 and 20 mg . kg(-1)) were ineffective in producing pleurod esis. From this study, we conclude that the intrapleural injection of 0.8 mg . kg(-1) of nitrogen mustard produces clinically significant pl eurodesis in rabbits. Consideration should be given to future clinical studies utilizing 0.6-0.8 mg . kg(-1) nitrogen mustard intrapleurally for the treatment of malignant pleural effusion.