Pleural effusion in patients with chronic myelogenous leukemia treated with dasatinib after imatinib failure.
OBJECTIVE
We investigated the risk factors and management of pleural effusion associated with dasatinib therapy for chronic myelogenous leukemia (CML) after failure of imatinib.


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.


CONCLUSIONS
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.
Quintás-Cardama
Alfonso
A
Department of Leukemia and Department of Radiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. aquintas@mdanderson.org
Kantarjian
Hagop
H
O'brien
Susan
S
Borthakur
Gautham
G
Bruzzi
John
J
Munden
Reginald
R
Cortes
Jorge
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D000069439:Dasatinib; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010879:Piperazines / Q000627:therapeutic use*; D010996:Pleural Effusion / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000517:prevention & control; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use*; D011859:Radiography; D012307:Risk Factors; D013844:Thiazoles / Q000009:adverse effects* / Q000627:therapeutic use*; D017211:Treatment Failure
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D000069439:Dasatinib