Bleomycin-induced lung injury
- Darren Feldman, MD
Darren Feldman, MD
- Assistant Attending Physician,
- Department of Medicine,
- Memorial Sloan Kettering Cancer Center
- Assistant Professor in Medicine,
- Weill Cornell Medical College
- Nicholas Vander Els, MD
Nicholas Vander Els, MD
- Assistant Professor of Medicine
- Cornell University Medical College
- Section Editor
- Philip W Kantoff, MD
Philip W Kantoff, MD
- Section Editor — Testicular Cancer
- Chairman of Medicine
- Memorial Sloan Kettering Cancer Center
- Deputy Editors
- Helen Hollingsworth, MD
Helen Hollingsworth, MD
- Deputy Editor — Pulmonary, Critical Care, and Sleep Medicine
- Associate Professor of Medicine
- Boston University School of Medicine
- Diane MF Savarese, MD
Diane MF Savarese, MD
- Senior Deputy Editor — UpToDate
- Deputy Editor — Oncology and Palliative Care
- Clinical Instructor of Medicine
- Harvard Medical School
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, predominantly germ cell tumors and 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 in patients receiving chemotherapy are presented separately. (See "Approach to the immunocompromised patient with fever and pulmonary infiltrates" and "Pulmonary toxicity associated with systemic antineoplastic therapy: Clinical presentation, diagnosis, and treatment".)
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.
Oxidative damage to the lung appears important in the pathophysiology of lung injury, and antioxidants may ameliorate the process [4,8]. Depletion of iron with chelators also reduces the toxicity of bleomycin both in vitro and in vivo, probably secondary to decreased production of free radicals [4,9,10].
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- Germ cell and ovarian sex cord stromal tumors
- Hodgkin lymphoma
- RISK FACTORS
- Dose and renal insufficiency
- Other chemotherapy and radiation therapy
- High fraction of inspired oxygen
- Cigarette smoking
- Colony stimulating factors
- SCREENING ASYMPTOMATIC PATIENTS FOR LUNG TOXICITY
- CLINICAL PRESENTATION
- EVALUATION OF PATIENTS WITH SUSPECTED PULMONARY TOXICITY
- Pulmonary function testing
- Bronchoalveolar lavage
- Lung biopsy
- - Pathology
- DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS
- Permanent discontinuation of bleomycin
- Glucocorticoids for lung toxicity
- Supplemental oxygen and future perioperative management
- SUMMARY AND RECOMMENDATIONS