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
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.