A prospective study of pulmonary function in patients receiving mitomycin

Mitomycin is a chemotherapeutic agent that is used to treat a variety of solid tumors. Pulmonary toxic reactions from this agent can be life threatening. We prospectively investigated the utility of pulmonary function tests (PFTs) in monitoring for the occurrence of pulmonary toxicity due to mitomycin. PFTs were obtained at baseline and after three cycles of mitomycin therapy. We analyzed the clinical course, radiologic studies, and PFT results in 133 patients with metastatic squamous cell carcinoma of the lung randomized to treatment with either mitomycin, vinblastine, and cisplatin or mitomycin alone as part of a prospective treatment protocol of the North Central Cancer Treatment Group (NCCTG). The diffusing capacity (Dco) was available in only 40 patients after the third cycle due to a high rate of progression and death from their underlying disease. After three cycles of chemotherapy, there was an average decline in the Dco of 14% (p<0.0001) and no changes were observed in expiratory flows. No differences were noted between treatment arms. A significant decline in the Dco (defined as a >20% change after correcting for hemoglobin) was noted in 11 of 40 patients (28%). This decline in the Dco was not associated with a worse prognosis (p=0.77), Seven patients (5%) developed severe pulmonary toxic reactions attributed to chemotherapy, including noncardiogenic pulmonary edema, interstitial pneumonitis, and pleural effusions. Corticosteroid therapy resulted in temporary subjective improvement in three patients. The Dco did not correlate with the development of pulmonary toxic reactions in these seven patients. In conclusion, (1) the incidence of clinically significant pulmonary toxic reactions from mitomycin is relatively low (5%), (2) mitomycin therapy resulted in a greater than 20% decline in the Dco in approximately one-fourth of patients receiving three cycles of chemotherapy, and (3) the use of serial PFTs in patients receiving mitomycin was not shown to be predictive of pulmonary toxicity.