title: Dasatinib 100 mg once daily minimizes the occurrence of pleural effusion in patients with chronic myeloid leukemia in chronic phase and efficacy is unaffected in patients who develop pleural effusion.
abstract: BACKGROUND
  Dasatinib, a highly potent BCR-ABL inhibitor, is an effective treatment for patients with chronic myeloid leukemia in chronic phase (CML CP) after resistance, suboptimal response, or intolerance to prior imatinib. In a phase 3 dose optimization trial in patients with CML CP (CA180-034), the occurrence of pleural effusion was significantly minimized with dasatinib 100 mg once daily (QD) compared with other treatment arms (70 mg twice daily [twice daily], 140 mg QD, or 50 mg twice daily).
  
  
  METHODS
  To investigate the occurrence and management of pleural effusion during dasatinib treatment, and efficacy in patients with or without pleural effusion, data from CA180-034 were analyzed.
  
  
  RESULTS
  With 24-month minimum follow-up, 14% of patients treated with dasatinib 100 mg QD incurred pleural effusion (grade 3: 2%; grade 4: 0%) compared with 23% to 26% in other study arms. The pleural effusion rate showed only a minimal increment from 12 to 24 months. In the 100 mg QD study arm, median time to pleural effusion (any grade) was 315 days, and after pleural effusion, 52% of patients had a transient dose interruption, 35% had a dose reduction, 57% received a diuretic, and 26% received a corticosteroid. Three patients in the 100 mg QD study arm discontinued treatment after pleural effusion. Across all study arms, patients with or without pleural effusion demonstrated similar progression-free and overall survival, and cytogenetic response rates were higher in patients with a pleural effusion.
  
  
  CONCLUSIONS
  Pleural effusion is minimized with dasatinib 100 mg QD dosing and its occurrence does not affect short- or long-term efficacy.
authors.affiliation: Hematology Research Unit, Biomedicum Helsinki, Helsinki University Central Hospital, P.O. Box 700, FIN-00029 HUCH, Helsinki, Finland. kimmo.porkka@helsinki.fi
authors.forename: Kimmo
authors.initials: K
authors.lastname: Porkka
authors.forename: H Jean
authors.initials: HJ
authors.lastname: Khoury
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Paquette
authors.forename: Yousif
authors.initials: Y
authors.lastname: Matloub
authors.forename: Ritwik
authors.initials: R
authors.lastname: Sinha
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000069439:Dasatinib; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015466:Leukemia, Myeloid, Chronic-Phase / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics; D008875:Middle Aged; D010996:Pleural Effusion / Q000150:complications / Q000517:prevention & control* / Q000628:therapy; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D012307:Risk Factors; D013844:Thiazoles / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000069439:Dasatinib