Mitomycin lung toxicity. Acute and chronic phases

Pulmonary toxicity is a rare but well described side effect of mitomycin C (MMC). We describe 14 cases of MMC pulmonary toxicity that were detected in four clinical trials performed at The Mayo Clinic using MMC-containing regimens for nonsmall cell lung cancer (NSCLC) and by reviewing the charts of patients treated at The Mayo Clinic with MMC-containing regimens for NSCLC from 1976 to 1995. The median age was 61 (range 44-84) years, with an M:F ratio of 1:1. The median number of cycles of MMC to develop toxicity was four (range two to five) with a median cumulative dose of MMC of 29 mg/m2. MMC toxicity occurred despite pre-medication with corticosteroids in 11 patients. At diagnosis of MMC lung toxicity, the median diffusing lung capacity (DLCO) was 9 and PaO2 was 49 mm Hg. Of those having bronchoscopy, four patients had pulmonary histologic changes consistent with lung injury. Two patients had bronchioalveolar lavages that were nondiagnostic. All patients responded initially to corticosteroids, but approximately 40% had progressive pulmonary insufficiency despite high doses of corticosteroids. This chronic, progressive phase of MMC lung toxicity is a largely underestimated sequelae of MMC.