title: Cyclophosphamide versus placebo in scleroderma lung disease.
abstract: BACKGROUND
  We conducted a double-blind, randomized, placebo-controlled trial to determine the effects of oral cyclophosphamide on lung function and health-related symptoms in patients with evidence of active alveolitis and scleroderma-related interstitial lung disease.
  
  
  METHODS
  At 13 clinical centers throughout the United States, we enrolled 158 patients with scleroderma, restrictive lung physiology, dyspnea, and evidence of inflammatory interstitial lung disease on examination of bronchoalveolar-lavage fluid, thoracic high-resolution computed tomography, or both. Patients received oral cyclophosphamide (< or =2 mg per kilogram of body weight per day) or matching placebo for one year and were followed for an additional year. Pulmonary function was assessed every three months during the first year, and the primary end point was the forced vital capacity (FVC, expressed as a percentage of the predicted value) at 12 months, after adjustment for the baseline FVC.
  
  
  RESULTS
  Of 158 patients, 145 completed at least six months of treatment and were included in the analysis. The mean absolute difference in adjusted 12-month FVC percent predicted between the cyclophosphamide and placebo groups was 2.53 percent (95 percent confidence interval, 0.28 to 4.79 percent), favoring cyclophosphamide (P<0.03). There were also treatment-related differences in physiological and symptom outcomes, and the difference in FVC was maintained at 24 months. There was a greater frequency of adverse events in the cyclophosphamide group, but the difference between the two groups in the number of serious adverse events was not significant.
  
  
  CONCLUSIONS
  One year of oral cyclophosphamide in patients with symptomatic scleroderma-related interstitial lung disease had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and the health-related quality of life. The effects on lung function were maintained through the 24 months of the study.
authors.affiliation: University of California at Los Angeles, Los Angeles, USA. dtashkin@mednet.ucla.edu
authors.forename: Donald P
authors.initials: DP
authors.lastname: Tashkin
authors.forename: Robert
authors.initials: R
authors.lastname: Elashoff
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Clements
authors.forename: Jonathan
authors.initials: J
authors.lastname: Goldin
authors.forename: Michael D
authors.initials: MD
authors.lastname: Roth
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
authors.forename: Edgar
authors.initials: E
authors.lastname: Arriola
authors.forename: Richard
authors.initials: R
authors.lastname: Silver
authors.forename: Charlie
authors.initials: C
authors.lastname: Strange
authors.forename: Marcy
authors.initials: M
authors.lastname: Bolster
authors.forename: James R
authors.initials: JR
authors.lastname: Seibold
authors.forename: David J
authors.initials: DJ
authors.lastname: Riley
authors.forename: Vivien M
authors.initials: VM
authors.lastname: Hsu
authors.forename: John
authors.initials: J
authors.lastname: Varga
authors.forename: Dean E
authors.initials: DE
authors.lastname: Schraufnagel
authors.forename: Arthur
authors.initials: A
authors.lastname: Theodore
authors.forename: Robert
authors.initials: R
authors.lastname: Simms
authors.forename: Robert
authors.initials: R
authors.lastname: Wise
authors.forename: Fredrick
authors.initials: F
authors.lastname: Wigley
authors.forename: Barbara
authors.initials: B
authors.lastname: White
authors.forename: Virginia
authors.initials: V
authors.lastname: Steen
authors.forename: Charles
authors.initials: C
authors.lastname: Read
authors.forename: Maureen
authors.initials: M
authors.lastname: Mayes
authors.forename: Ed
authors.initials: E
authors.lastname: Parsley
authors.forename: Kamal
authors.initials: K
authors.lastname: Mubarak
authors.forename: M Kari
authors.initials: MK
authors.lastname: Connolly
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Golden
authors.forename: Mitchell
authors.initials: M
authors.lastname: Olman
authors.forename: Barri
authors.initials: B
authors.lastname: Fessler
authors.forename: Naomi
authors.initials: N
authors.lastname: Rothfield
authors.forename: Mark
authors.initials: M
authors.lastname: Metersky
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007970:Leukopenia / Q000139:chemically induced; D017563:Lung Diseases, Interstitial / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012129:Respiratory Function Tests; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide