The pulmonary toxicity of nitrosoureas

Drug-induced pulmonary fibrosis in cancer chemotherapy has become a more serious problem as treatment regimens are refined, larger total doses of cytotoxic drugs are administered and patient prognosis improves. The nitrosoureas are a class of chemotherapeutic agents whose clinical use is severely limited by drug-induced toxicities. The myelosuppression caused by nitrosourea administration can be managed clinically; however, the development of irreversible pulmonary fibrosis is a more serious clinical problem. Studies are needed to identify biochemical markers for early lung injury so that the amount of pulmonary tissue damage can be assessed and monitored. Additionally, considerable research is needed to understand the mechanisms by which these agents produce lung injury, so that therapeutic regimens can be developed to minimize or prevent lung toxicity. In understanding the mechanisms of toxicity, potentially the pulmonary injury caused by nitrosourea administration can be altered without affecting the clinical antitumor activity of this class of compounds. In the future, knowledge on mechanisms of drug-induced pulmonary injury can be used in the development of antineoplastic agents which are more disease specific and less pulmonary toxic.