Bleomycin is an antitumor antibiotic that was isolated from a strain of Streptomyces verticillus in 1966 . It has been used successfully to treat a variety of malignancies, including squamous cell carcinoma of the head and neck, cervix, and esophagus; germ cell tumors; and both Hodgkin and non-Hodgkin lymphoma.
The major limitation of bleomycin therapy is the potential for life-threatening interstitial pulmonary fibrosis (also called fibrosing alveolitis) in up to 10 percent of patients receiving the drug [2-5]. Other, less common forms of lung injury include organizing pneumonia and hypersensitivity pneumonitis .
The pathogenesis and clinical aspects of bleomycin-induced lung injury will be reviewed here. Potential drug interactions that may modify the course of bleomycin-induced lung injury and the therapeutic options available for management will also be discussed. A general approach to immunocompromised patients with respiratory symptoms and the evaluation of interstitial lung disease are presented separately. (See "Approach to the immunocompromised patient with fever and pulmonary infiltrates".)
The antineoplastic effect of bleomycin is unique among anticancer agents, and is thought to involve the production of single- and double-strand breaks in DNA (scission) by a complex of bleomycin, ferrous ions, and molecular oxygen [2,6,7]. Bleomycin binds to DNA by intercalation of the bithiazole moiety between base pairs of DNA and by electrostatic interactions of the terminal amines. The reduction of molecular oxygen by ferrous ions chelated by bleomycin leads to hydrogen subtraction from the C3 and C4 carbons of deoxyribose, resulting in cleavage of the C3-C4 bond and liberation of a base with a DNA strand break . Bleomycin is inactivated in vivo by the enzyme bleomycin hydrolase, a cytosolic aminopeptidase that has lower activity in the skin and lungs.
The mechanism of bleomycin-induced lung injury is not entirely clear, but likely includes components of oxidative damage, relative deficiency of the deactivating enzyme bleomycin hydrolase, genetic susceptibility, and elaboration of inflammatory cytokines.