title: Phase II study of dasatinib in patients with previously treated malignant mesothelioma (cancer and leukemia group B 30601): a brief report.
abstract: BACKGROUND
  We conducted a phase II trial of dasatinib in malignant mesothelioma (MM) patients to evaluate its toxicity and efficacy as a second-line treatment.
  
  
  METHODS
  Patients with unresectable MM and no symptomatic effusions were given dasatinib 70 mg twice daily as part of a 28-day cycle. We also measured plasma vascular endothelial growth factor and platelet-derived growth factor b and colony stimulating factor 1 (CSF-1) and mesothelin-related protein at baseline and during therapy.
  
  
  RESULTS
  Forty-six patients were enrolled in this study. Fifty percent of the first 12 patients enrolled experienced ≥grade 3 treatment-related adverse events, and therefore, the starting dose was reduced to 50 mg twice daily. Grade 3 and 4 toxicities included fatigue (11%) and pleural effusion (9%). The overall disease control rate was 32.6%, and progression-free survival at 24 weeks was 23% (95% confidence interval: 13.5-40.0%). Survival was markedly longer in patients with lower pretreatment CSF-1 levels and in patients whose CSF-1 levels decreased from baseline during therapy.
  
  
  CONCLUSIONS
  Single-agent dasatinib has no activity in MM and is associated with pulmonary toxicities that prohibit its use in an unselected MM population.
authors.affiliation: Department of Medicine, University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA. dudek002@umn.edu
authors.forename: Arkadiusz Z
authors.initials: AZ
authors.lastname: Dudek
authors.forename: Herbert
authors.initials: H
authors.lastname: Pang
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kratzke
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Otterson
authors.forename: Lydia
authors.initials: L
authors.lastname: Hodgson
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Hedy L
authors.initials: HL
authors.lastname: Kindler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000069439:Dasatinib; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000401:mortality; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D016173:Macrophage Colony-Stimulating Factor; D000069439:Dasatinib