Intermittent intravenous cyclophosphamide pulse therapy for the treatment of active interstitial lung disease associated with collagen vascular diseases.

The availability of intravenous cyclophosphamide (CYC) pulse therapy for collagen vascular diseases (CVD)-associated interstitial lung disease (ILD) has been indicated. However, the standard protocol concerning the dosage and the interval of CYC infusion has not yet been established. The aim of this study is to elucidate the efficacy and the safety of our "divided administration" protocol of CYC for the treatment of CVD-ILD. The treatment protocol consists of two steps: step 1, CYC 400-500 mg at 10-day intervals for at least 30 days, and step 2, CYC 500 mg at 14-day intervals for at least 4 weeks. The ILD activities were monitored by respiratory symptoms, serum levels of KL-6 (a serological marker of IP), chest computed tomography (CT), and pulmonary function tests. Seventeen patients [nonspecific interstitial pneumonia (NSIP), 12 patients; usual interstitial pneumonia (UIP), 4; lymphocytic interstitial pneumonia (LIP), 1] accomplished the study protocol. The sessions of CYC infusion ranged from 5 to 20 (mean, 8.3). In all patients, respiratory symptoms were improved and the serum levels of KL-6 were decreased (from 1572 +/- 904 to 978 +/- 392 U/ml; P < 0.01). Chest CT findings were improved in 4 patients (23.5%): they were all classified as NSIP; not deteriorated, 13 patients (76.5%). An improvement in the vital capacity percentage (%VC) was recognized in 10 patients (78.6%) and in diffusing capacity of carbon monoxide (%DLco) in 8 patients (61.5%). Nevertheless, mean %VC and mean %DLco did not change significantly. No major adverse event(s) occurred. The efficacy and safety of our "divided administration" protocol of CYC for CVD-ILD was demonstrated.