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Cyclophosphamide pulmonary toxicity

INTRODUCTION

Cyclophosphamide is an immunosuppressive alkylating agent that is used in combination with other chemotherapeutic agents for the treatment of a variety of malignant processes. It is also increasingly used for the treatment of certain autoimmune diseases, either as a sole agent or in combination with corticosteroids. Unfortunately, long-term use of cyclophosphamide is associated with a multitude of significant side effects, such as hair loss, leukopenia, hemorrhagic cystitis, infertility, the development of secondary malignancies, and pulmonary toxicity.

The pathogenesis, clinical manifestations, diagnosis, and treatment of cyclophosphamide pulmonary toxicity will be presented here. Other toxicities of cyclophosphamide are discussed separately. (See "General toxicity of cyclophosphamide and chlorambucil in inflammatory diseases" and "General principles of the use of cyclophosphamide in rheumatic and renal disease".)

CLINICAL FEATURES

Cyclophosphamide-induced pulmonary injury appears to be rare. However, the risk may be increased by the concomitant use of radiation, oxygen therapy, or other drugs with potential pulmonary toxicity; these factors also may confound attempts to estimate the incidence of pure cyclophosphamide-induced lung injury.

There are two distinct clinical patterns of pulmonary toxicity associated with cyclophosphamide: an acute pneumonitis that occurs early in the course of treatment; and a chronic, progressive, fibrotic process that may occur after prolonged therapy [1]. A single case of acute pulmonary edema after intravenous cyclophosphamide also has been reported [2].

Early-onset pneumonitis — Affected patients present with cough and dyspnea within one to six months after the onset of therapy; fever and fatigue also may be present [1,3]. Chest radiographs and CT scans can show interstitial inflammation and/or a ground glass appearance. Discontinuation of the drug and institution of corticosteroids usually result in complete restoration of lung function in this syndrome.

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Last literature review version 18.2: May 2010
This topic last updated: February 25, 2008
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References
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Cyclophosphamide pulmonary toxicity Urine anion and osmolal gaps in metabolic acidosis