Abstract
Dasatinib is a potent second-generation tyrosine kinase inhibitor approved for the treatment of chronic myeloid leukemia after imatinib failure. However, some patients treated with dasatinib experience pleural effusions (PEs). The determinants of pleural effusion in long-term dasatinib treatment (median 35 months, range 1–55) were investigated in single-center data of 65 patients enrolled in global phase 2 and phase 3 trials. Of the 65 patients, 35 (54%) developed dasatinib-induced pleural effusion (a median onset time, 20 months; range 0.2–54). The first pleural effusion developed in 15 (43%) patients within 12 months of dasatinib therapy. Disease phase (P = 0.02), dose schedule (P = 0.002) and actual daily mean dose (P = 0.0002) were significantly associated with an increased risk of pleural effusion. Twice-daily administration of dasatinib resulted in significantly more patients developing pleural effusions compared with the once-daily dosing schedule, particularly in advanced disease. In addition, a strong correlation was found between actual daily mean dose and time to onset of pleural effusions in patients treated with a daily mean dose >100 mg/day of dasatinib (P = 0.01). These data emphasize the need for dasatinib dose and schedule optimization and long-term monitoring of dasatinib-treated patients to prevent the negative clinical implications of pleural effusion.
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Acknowledgments
This study was supported by research grants from Bristol-Myers Squibb, the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (01-PJ10-PG6-01GN16-0005) and from the Basic Research Program of the Korea Science and Engineering Foundation (R21-2007-000-10041-0) (2007). We thank Daniel Hutta, PhD, and Candice Willmon, PhD, for medical editorial assistance with this manuscript.
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Effect of administration schedule on cumulative incidence of pleural effusion in CP only (a), in AP only (b), and in BC only (c). AP, accelerated phase; BC, blast crisis; BID, twice daily; CP, chronic phase; QD, once daily (JPEG 34 kb)
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Effect of actual daily mean dose on cumulative percentage of pleural effusion development during dasatinib therapy in CP only (a), in AP only (b, and in BC only (c) (JPEG 39 kb)
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Event-free survival of patients with or without pleural effusion in all disease phases (a) and in chronic phase (b). Events include death, disease progression, loss of complete hematologic response and loss of major cytogenetic response (JPEG 28 kb)
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Kim, D., Goh, HG., Kim, SH. et al. Long-term pattern of pleural effusion from chronic myeloid leukemia patients in second-line dasatinib therapy. Int J Hematol 94, 361–371 (2011). https://doi.org/10.1007/s12185-011-0921-9
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DOI: https://doi.org/10.1007/s12185-011-0921-9