EMPIRIC PREDNISONE THERAPY FOR PULMONARY TOXIC REACTION AFTER HIGH-DOSE CHEMOTHERAPY CONTAINING CARMUSTINE (BCNU)

Study objective: To determine pretreatment factors that predict for pu lmonary toxic reactions after high-dose chemotherapy containing carmus tine (BCNU) and to determine the utility of prednisone in preventing p ulmonary toxic reactions. Design: Retrospective review. Setting: Terti ary care referral center. Patients: Forty-five patients with relapsed or refractory lymphoma and 27 patients with breast cancer with normal cardiopulmonary function were treated with one of two high-dose combin ation chemotherapeutic regimens containing the same dose of BCNU. Meas urements: Recorded pretreatment patient characteristics included previ ous chemotherapy or radiation therapy, history of pulmonary metastases , history of chronic obstructive pulmonary disease, and history of smo king. Spirometry and single-breath carbon monoxide diffusing capacity (Dco) were obtained before and after high-dose chemotherapy. Intervent ions: Patients were treated with prednisone for a 5% or more drop in p ostchemotherapy Dco whether or not symptoms were present, Results: Fif ty-nine patients were evaluable. No pretreatment characteristic predic ted for declines in pulmonary function postchemotherapy. The FEV(1)/FV C ratio did not change significantly after high-dose chemotherapy, but the Dco decreased 12.1% (p<0.001). Of the 59 eval uable patients, 30 were treated with prednisone for declines in postchemotherapy Dco. Six teen (53%) of these 30 patients were asymptomatic. The Dco increased 1 0.3%, in patients treated with prednisone compared with a decrease of 2.3% in patients not treated (p = 0.017). There was no statistically s ignificant difference in FEV(1)/FVC in patients treated with prednison e compared with those not treated. Regression analysis of pretreatment characteristics, type of high-dose chemotherapy received, and treatme nt with prednisone identified only treatment with prednisone as a sign ificant variable in predicting an increase in Dco (p = 0.03; regressio n coefficient = +11.5%;, SE = +/-5.2%) after high-dose chemotherapy co ntaining BCNU. Conclusions: High-dose BCNU-containing chemotherapeutic regimens cause decreases in Dco that are often asymptomatic and likel y represent subclinical pulmonary toxic reactions. Pretreatment clinic al parameters cannot predict which patients will manifest pulmonary to xic reactions after high-dose chemotherapy. Empiric treatment with pre dnisone will reverse chemotherapy-induced decreases in Dco. Earlier in stitution of glucocorticoids for evidence of pulmonary dysfunction is recommended.