Pleural effusion in patients with chronic myelogenous leukemia treated with dasatinib after imatinib failure

J Clin Oncol. 2007 Sep 1;25(25):3908-14. doi: 10.1200/JCO.2007.12.0329.

Abstract

Purpose: We investigated the risk factors and management of pleural effusion associated with dasatinib therapy for chronic myelogenous leukemia (CML) after failure of imatinib.

Patients and methods: We analyzed 138 patients with CML treated with dasatinib from November 2003 to January 2006 in one phase I (n = 50) and four phase II (n = 88) studies for the development of pleural effusion.

Results: Pleural effusion occurred in 48 patients (35%; grade 3/4 in 23 [17%]), including 29% of those treated in chronic phase (CP), 50% in accelerated phase (AP), and 33% in blast phase (BP). By multivariate analysis, history of cardiac disease, hypertension, and use of a twice-daily schedule (v once daily) were identified as factors associated with development of pleural effusions. Effusions were exudative in 78% of the assessable cases. In some patients, effusions were associated with reversible increments of right ventricular systolic pressure. Management included transient dasatinib interruption in 83%, diuretics in 71%, pulse steroids in 27%, and thoracentesis in 19% of patients.

Conclusion: Pleural effusions occur during dasatinib therapy, particularly among patients in AP or BP. A twice-daily schedule may result in a higher incidence of pleural effusion. Close monitoring and timely intervention may allow patients to continue therapy and achieve the desired clinical benefit.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Benzamides
  • Dasatinib
  • Drug Administration Schedule
  • Drug Monitoring
  • Female
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Piperazines / therapeutic use*
  • Pleural Effusion / chemically induced*
  • Pleural Effusion / diagnostic imaging
  • Pleural Effusion / prevention & control
  • Pyrimidines / adverse effects*
  • Pyrimidines / therapeutic use*
  • Radiography
  • Risk Factors
  • Thiazoles / adverse effects*
  • Thiazoles / therapeutic use*
  • Treatment Failure

Substances

  • Benzamides
  • Piperazines
  • Pyrimidines
  • Thiazoles
  • Imatinib Mesylate
  • Dasatinib