LUNG TOXICITY ASSOCIATED WITH CYCLOPHOSPHAMIDE USE - 2 DISTINCT PATTERNS

Cyclophosphamide-induced lung toxicity may be difficult to recognize b ecause of the presence of confounding variables such as concomitant us e of other cytotoxic drugs, opportunistic infections, diffuse pulmonar y malignancy, radiation pneumonitis, and oxygen toxicity. The purpose of this retrospective analysis was to identify the clinical spectrum o f pulmonary toxicity of cyclophosphamide. In our review of case record s, we sought to identify patients in whom cyclophosphamide was the onl y identifiable etiologic factor for lung toxicity. In a 20-yr period s ix patients were identified with cyclophosphamide-induced lung disease , including five men and one woman ranging in age from 42 to 78 yr. Cl inical features of toxicity include dyspnea, fever, cough, new parench ymal infiltrates, gas exchange abnormalities on pulmonary function tes ts, and pleural thickening on chest roentgenogram Two patterns of cycl ophosphamide-induced lung toxicity were identified. A single patient p resented with early-onset pneumonitis and responded to discontinuation of the drug. Five patients with late-onset pneumonitis developed prog ressive pulmonary fibrosis associated with bilateral pleural thickenin g. Patients with late-onset pneumonitis showed no response to cessatio n of cyclophosphamide and institution of corticosteroid therapy. Three of these patients died of respiratory failure. Careful review of the individual cases reported in the literature as cyclophosphamide lung t oxicity revealed only 12 cases in whom none of the additional confound ing factors could be identified. These could easily be divided in the same two categories. Early-onset pneumonitis is reversible and may res pond to corticosteroid therapy. Late-onset pneumonitis, frequently ass ociated with pleural thickening, is clinically distinct from idiopathi c pulmonary fibrosis but has a chronically progressive course. It appe ars unresponsive to corticosteroid therapy.