Chemotherapy-induced interstitial pneumonitis during treatment of small cell anaplastic lung cancer.

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Abstract
Twelve cases of interstitial pneumonitis were seen in 50 patients (24%) treated with cyclophosphamide, methotrexate and etoposide (VP-16-213) for small cell anaplastic lung cancer. The clinical course and pathologic characteristics were consistent with drug-induced pneumonitis in all 12 cases. One additional patient had concurrent histologic evidence of interstitial pneumonitis, pneumocystis infection, and perivascular metastases. Patients presented with severe dyspnea, hypoxemia, cough, fever and bilateral interstitial infiltrates on chest films. The onset was rapid and unpredictable, following as little as 1 mo. or as much as 5 mo. of therapy. Nine patients recovered but there were 3 deaths in the acute period directly attributable to the drug-induced pneumonitis. Although the use of twice weekly oral methotrexate may have been a causative factor, a previously unsuspected drug interaction with etoposide may be the etiologic factor resulting in this unusually high incidence of pulmonary toxicity. The difficulty in establishing a diagnosis of interstitial pneumonitis in this group of patients with chronic lung disease and lung cancer is well known. The extent of morbidity and mortality seen in this study and the commercial availability of etoposize make earlier clinical recognition of this complication imperative.