Comparison of mitoxantrone and tetracycline as pleural sclerosing agents in rabbits

Abstract

Bleomycin is the antineoplastic agent used most commonly for the treatment of malignant pleural effusion. It is absorbed rapidly from the pleural space and does not elicit pleurodesis in the normal rabbit pleura. Mitoxantrone is a new antineoplastic that differs from bleomycin in that it binds to membranes. Accordingly it might remain in the pleural space for a longer period and produce a pleurodesis. The objective of this project was to determine whether mitoxantrone is an effective sclerosant in an experimental model in rabbits. The following medications were instilled intrapleurally in anesthetized male rabbits: 35 mg/kg tetracycline or 0.5, 1.0, or 2.0 mg/kg mitoxantrone. The animals were killed at 28 days and the pleural spaces assessed grossly for pleurodesis and microscopically for fibrosis and inflammation. The mean degree of gross pleurodesis did not differ significantly in the rabbits that received tetracycline (3.8 +/- 0.4) and in the rabbits that received 2 mg/kg mitoxantrone (3.2 +/- 1.3). The degree of pleural and lung inflammation was significantly greater after mitoxantrone than after tetracycline, both ipsilaterally and contralaterally. The mortality after the highest dose of mitoxantrone was 50%. From this study we conclude that the intrapleural administration of mitoxantrone in rabbits can produce a pleurodesis. The histologic picture after mitoxantrone administration differs markedly from that after tetracycline injection. After mitoxantrone injection there are many more inflammatory cells present on the side that received the injection, and there is much more fibrosis and inflammation in the contralateral pleura and lung. The model of pleural fibrosis following intrapleural mitoxantrone may be useful for the study of pleural fibrosis.

Acute and Chronic Pleural Changes after the Intrapleural Instillation of Mitoxantrone in Rabbits

“…The degree of pleurodesis was comparable to that elicited by 35 mg/kg tetracycline [14]. Interestingly, however, the rabbits that received mitoxantrone had significantly more pleural and lung inflammation than did the rabbits receiving tetracycline [14].…”

“…In our previous study in which the rabbits received 2.0 mg/kg, the mortality rate was 50% at 28 days, and the rabbits also died of congestive heart failure with eosinophilic myocarditis [14]. The earlier mortality in the previous study was probably related to the higher dose of mitoxantrone.…”

“…We have shown previously that the intrapleural injection of 2.0 mg/kg mitoxantrone results in pleurodesis in rabbits after 28 days [14]. The degree of pleurodesis was comparable to that elicited by 35 mg/kg tetracycline [14].…”

“…A dose of 1.5 mg/kg was used in the present study because rabbits that were given 2.0 mg/kg had a high mortality, and rabbits that were given 1.0 mg/kg had minimal changes in our previous study [14]. We studied two groups of animals; the first group (acute study) included 36 rabbits, and the second group (chronic study) included 34 different rabbits.…”

Pleural Sclerosis for the Treatment of Pneumothorax and Pleural Effusion

“…In patients treated with mitoxantrone for control of malignant pleural effusions, the success rate has averaged about 70% [8,26]. Mitoxantrone, in contrast, to bleomycin also produces pleurodesis in the rabbit [21,50]. Nitrogen mustard was one of the first agents used to produce a pleurodesis.…”