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The occurrence and management of fluid retention associated with TKI therapy in CML, with a focus on dasatinib

Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, University of Southern California Medical Center, 1441 Eastlake Ave Suite 7317, Los Angeles, CA 90033, USA.
Journal of Hematology & Oncology (Impact Factor: 4.93). 11/2009; 2:46. DOI: 10.1186/1756-8722-2-46
Source: PubMed

ABSTRACT Tyrosine kinase inhibitors (TKIs) like dasatinib and nilotinib are indicated as second-line treatment for chronic myeloid leukemia resistant or intolerant to the current first-line TKI imatinib. These are agents are well tolerated, but potent and as such should be monitored for potentially serious side-effects like fluid retention and pleural effusions. Here we present key clinical trial data and safety considerations for all FDA approved TKIs in context for effective management of fluid retention and pleural effusions. Altering the dasatinib regimen from 70 mg twice daily to 100 mg daily reduces the risk of pleural effusion for patients taking dasatinib. Should pleural effusion develop, dasatinib should be interrupted until the condition resolves. Patients with a history of pleural effusion risk factors should be monitored closely while taking dasatinib. Patients receiving imatinib and nilotinib are not without risk of fluid retention. All patients should also be educated to recognize and report key symptoms of fluid retention or pleural effusion. Pleural effusions are generally managed by dose interruption/reduction and other supportive measures in patients with chronic myeloid leukemia receiving dasatinib therapy.

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Available from: Allen S Yang, Sep 29, 2014
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    • "Oral medications for CML include tyrosine kinase inhibitors as imatinib, dasatinib, and nilotinib. The incidence of dasatinib related pleural effusion is about 7–35% [2]. While pleural effusions are seen less often with imatinib, those seen with nilotinib are very rare (<1%) [3]. "
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    ABSTRACT: Pleural effusion, as a side effect of tyrosine kinases, may be seen as most commonly associated with dasatinib and very rarely seen with nilotinib. In this report we present a chronic phase of CML case that was treated with nilotinib due to imatinib (Gleevec) allergy and had pleural effusion with nilotinib at 5th year of treatment. If pleural effusion develops in patients taking nilotinib and if this effusion is exudative and lymphocyte predominant, after ruling out pulmonary and cardiac etiologies, it must be associated with nilotinib; according to stage of effusion drug should be discontinued and/or steroid should be started and/or surgery should be performed.
    Case Reports in Medicine 09/2014; 2014:203939. DOI:10.1155/2014/203939
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    • "Dasatinib was initially proposed as a second-line therapy in chronic myeloid leukemia. Of note, pulmonary complications, and specifically pleural effusions, have been reported more frequently with dasatinib use compared with other TKIs (Bergeron, Rea et al. 2007, Quintas-Cardama, Kantarjian et al. 2007, Masiello, Gorospe et al. 2009). Recently, we reported a series of 9 cases of severe precapillary PAH confirmed by right heart catheterization, occurring in patients treated with dasatinib in France(Montani, Bergot et al. 2012).Median delay between initiation of dasatinib and PAH diagnosis was 34 months. "
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    • "Pleural effusion is rare with nilotinib and imatinib but is a more prominent side effect of dasatinib treatment [26,27]. In the DASISION trial, 10% of patients in the dasatinib arm had a pleural effusion whereas no patient receiving imatinib reported this AE. "
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    ABSTRACT: Imatinib, a tyrosine kinase inhibitor (TKI) of BCR-ABL, was the standard first-line therapy for chronic myeloid leukemia (CML) for almost 10 years. Dasatinib and nilotinib, two newer drugs with higher potency than imatinib against BCR-ABL and activity against most imatinib-resistant BCR-ABL mutations, have each shown superior efficacy compared with imatinib for first-line treatment of chronic-phase CML in randomized phase 3 trials. With 14 months follow-up time, available data suggest no obvious differences in efficacy between dasatinib and nilotinib. Compared with imatinib, dasatinib is associated with higher rates of pleural effusion and thrombocytopenia, but lower rates of edema, gastrointestinal AEs, musculoskeletal AEs, and rash. Nilotinib is associated with higher rates of dermatologic toxicity, headache, and biochemical abnormalities associated with hepatic and pancreatic toxicity compared with imatinib, but lower rates of edema, gastrointestinal AEs, muscle spasm, and neutropenia. Several studies have shown that poor adherence to imatinib detrimentally affects responses and should be considered in patients with a suboptimal response. The different dosing requirements of dasatinib (once daily with or without food) and nilotinib (twice daily with fasting) may be an additional factor in selecting frontline agents. This review compares and contrasts the three FDA approved first line TKI agents.
    Journal of Hematology & Oncology 11/2010; 3:47. DOI:10.1186/1756-8722-3-47 · 4.93 Impact Factor
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