title: Low-dose oral imatinib in the treatment of systemic sclerosis interstitial lung disease unresponsive to cyclophosphamide: a phase II pilot study.
abstract: BACKGROUND
  Pulmonary involvement represents a major cause of death of systemic sclerosis (SSc) patients. Recent data suggest that tyrosine kinase inhibitors, such as imatinib, may be a therapeutic option for SSc patients. However, preliminary published clinical trials were inconclusive about imatinib efficacy and showed side effects. The purpose of this study was to verify efficacy and tolerability of low-dose imatinib on interstitial lung disease in a cohort of SSc patients unresponsive to cyclophosphamide therapy.
  
  
  METHODS
  Thirty consecutive SSc patients with active pulmonary involvement, unresponsive to cyclophosphamide, were treated with imatinib 200 mg/day for 6 months followed by a 6-month follow-up. A "good response" was defined as an increase of forced vital capacity (FVC) by more of 15% and/or increase of diffusing capacity of carbon monoxide (DLCO) >15% and PaO2 > 90% of initial value and high-resolution computed tomography (HRCT)-scan pattern unchanged or improved.
  
  
  RESULTS
  Twenty-six patients completed the study. Three patients died and one patient was lost to follow-up. Four patients (15.32%) had a good response, 7 worsened and 15 had a stabilized lung disease. Overall, 19 (73.07%) patients had an improved or stabilized lung disease. After a 6-month follow-up, 12 (54.5%) of the 22 patients showed an improved or stabilized lung disease.
  
  
  CONCLUSIONS
  Lung function was stabilized in a large proportion of patients unresponsive to cyclophosphamide therapy and a beneficial outcome emerged from the analysis of HRCT lung scans. There was no significant improvement of skin involvement, and the low dose was well tolerated. These data provide useful suggestions to design future randomized clinical trials for SSc therapeutics.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00573326. Registered 13 December 2007.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fraticelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Gabrielli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pomponio
authors.forename: Gabriele
authors.initials: G
authors.lastname: Valentini
authors.forename: Silvia
authors.initials: S
authors.lastname: Bosello
authors.forename: Piersandro
authors.initials: P
authors.lastname: Riboldi
authors.forename: Maria
authors.initials: M
authors.lastname: Gerosa
authors.forename: Paola
authors.initials: P
authors.lastname: Faggioli
authors.forename: Roberto
authors.initials: R
authors.lastname: Giacomelli
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Del Papa
authors.forename: Roberto
authors.initials: R
authors.lastname: Gerli
authors.forename: Claudio
authors.initials: C
authors.lastname: Lunardi
authors.forename: Stefano
authors.initials: S
authors.lastname: Bombardieri
authors.forename: Walter
authors.initials: W
authors.lastname: Malorni
authors.forename: Angelo
authors.initials: A
authors.lastname: Corvetta
authors.forename: Gianluca
authors.initials: G
authors.lastname: Moroncini
authors.forename: Armando
authors.initials: A
authors.lastname: Gabrielli
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001549:Benzamides / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D017563:Lung Diseases, Interstitial / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D012129:Respiratory Function Tests; D012595:Scleroderma, Systemic / Q000150:complications / Q000188:drug therapy*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D007166:Immunosuppressive Agents; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D003520:Cyclophosphamide