Study objectives: To prospectively examine the role of cyclophosphamide in patients with idiopathic pulmonary fibrosis that is unresponsive to or intolerant of high-dose steroid treatment.
Design: Prospective study.
Setting: Tertiary referral center.
Patients: Nineteen patients with biopsy specimen-proven usual interstitial pneumonia who failed to respond (n = 16) or experienced adverse effects (n = 3) from corticosteroid treatment (1 mg/kg/d for 3 months).
Intervention: Steroid therapy was tapered quickly, and oral cyclophosphamide, 2 mg/kg/d, was prescribed (mean duration of treatment, 6.0 +/- 0.9 months).
Measurements and results: In 10 patients, response to therapy was determined by pretreatment and posttreatment clinical (dyspnea), radiographic (chest radiograph), and physiologic (pulmonary function, including exercise saturation) scores (CRP). Response was defined as a > 10-point drop in CRP; stable as +/- 10-point change in CRP; and nonresponders as > 10-point rise in CRP. In nine patients, physiologic criteria were used to assess response; significant changes in pulmonary function were defined as follows: total lung capacity, +/- 10% of baseline value; FVC, +/- 10% of baseline value, diffusion capacity of the lung for carbon monoxide, +/- 20% of baseline value; and resting pulse oximetry, +/- 4% of baseline value. Patients who died while receiving or shortly after discontinuing cyclophosphamide were classified as nonresponders (n = 2). Among 19 patients treated with cyclophosphamide, only 1 patient demonstrated sustained response; 7 patients remained stable and 11 deteriorated while receiving the drug. Toxicity associated with cyclophosphamide was substantial; more than two thirds of the patients developed drug-related adverse effects, and almost half discontinued the drug prematurely due to side effects. In the remaining patients, cyclophosphamide therapy was discontinued due to lack of improvement or progressive deterioration.
Conclusions: Cyclophosphamide therapy is of limited efficacy in patients with idiopathic pulmonary fibrosis who fail to respond or who experience adverse effects from corticosteroid treatment, and adverse effects often complicate its use.