Nonbacterial pneumonitis with multidrug antineoplastic therapy in breast carcinoma

Seventeen patients with metastatic breast carcinoma were treated with a combination of 5-fluorouracil, methotrexate, vincristine, cyclophosphamide and prednisone. Six of the patients (35%) developed a syndrome consisting of fever, malaise, dyspnea, hypoxemia and bilateral pulmonary interstitial infiltrates from 41 to 148 days after institution of therapy. The syndrome varied from a mild to a life-threatening illness with recovery in 10 to 60 days. It is believed that these cases represent examples of methotrexate-induced pneumonitis. The high incidence of the syndrome in this patient group may be related to the concomitant administration of cyclophosphamide with methotrexate. The observations also suggest that patients with previous adrenalectomies may have pneumonitis with an especially severe and protracted course.