The pulmonary toxicity of antineoplastic agents.

Abstract

P ULMONARY TOXICITY has been associated with a variety of chemotherapeutic agents. Generally it is infrequent and sporadic, but there are exceptions to this rule. The two major exceptions include the total dose related pulmonary toxicity of bleomycin’ and the more recently appreciated cumulative dose related pulmonary toxicity of the nitrosoureas.’ The final common expression of lung injury appears to be pulmonary fibrosis. Histologically it is difficult, if not impossible, to differentiate bleomycin lung from idiopathic diffuse interstitial pulmonary fibrosis. Since the pathologic lesion associated with bleomycin has been most extensively studied, and because similar changes have been described for most agents, it will be described first. Bleomycin is a pulmonary toxin in many mammalian species, including rodents, dogs, monkeys and man. As a result the development of bleomytin pulmonary toxicity has been studied in both animal and human systems. Adamson’ has shown that soon after bleomycin administration endothelial blebs develop in mouse alveolar capillary endothelium. Similar observations have not been made in all species, and not in man, but this discrepancy may be more a function of experimental design than species specificity, The blebs are followed by the development of interstitial fibrinous edema, a mononuclear cell response, and hyaline membranes. Electron microscopic studies in man have shown a decrease in Type I pneumocytes and a subsequent change in Type II pneumocytes including proliferation, delamellation and migration into alveolar sacs. Finally, the