Pleural/pericardic effusions during dasatinib treatment: incidence, management and risk factors associated to their development

Breccia, Massimo

doi:10.1517/14740331003742935

Cited by 25 publications

(15 citation statements)

References 50 publications

(20 reference statements)

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“…15 The pathogenesis is likely multi-factorial, and is possibly due to tyrosine-kinase inhibition or immune-mediated effects involving other tyrosine kinases (TEC or BTK of lymphocyte B and T signaling). 7 The management of this side effect includes therapy interruption, drug dose reduction, steroids and diuretics and, only in a few severe instances, therapeutic thoracentesis.…”

Section: Discussionmentioning

confidence: 99%

“…7 The management of this side effect includes therapy interruption, drug dose reduction, steroids and diuretics and, only in a few severe instances, therapeutic thoracentesis. 6,7,15 Data from a phase III trial showed a slight increase of the incidence of this side effect over time, but not of grade 4 cases, after a follow-up of 3 years. 5 With adequate management and monitoring of patients with predisposing factors, the majority of individuals can continue therapy with the drug, even in the presence of this complication.…”

Section: Discussionmentioning

confidence: 99%

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Charlson comorbidity index and adult comorbidity evaluation-27 scores might predict treatment compliance and development of pleural effusions in elderly patients with chronic myeloid leukemia treated with second-line dasatinib

Breccia¹,

Latagliata²,

Stagno³

et al. 2011

Haematologica

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BackgroundComorbidities may affect survival and choice of treatment among cancer patients. In fact, comorbidities have been identified as significant determinants of response to therapy in older patients with acute myeloid leukemia, breast cancer, head and neck cancer, and lung cancer. The Charlson comorbidity index and adult comorbidity evaluation-27 are lists of comorbidities with a weight assigned from 1 to 6 for the former and from 0 to 3 for the latter score, derived from relative risk estimates of a proportional hazard regression model using clinical data. Design and MethodsWe retrospectively evaluated the Charlson index and adult comorbidity evaluation-27 score in a cohort of 125 elderly (> 60 years) patients with chronic phase chronic myeloid leukemia who received dasatinib after showing resistance or intolerance to imatinib with the aim of establishing associations between comorbidities and the development of pleural effusions or compliance with the drug treatment. ResultsWe found a significant association between the Charlson index as well as the adult comorbidity evaluation-27 score and the rate of drug reduction or suspension: with regards to the Charlson index, 49% of score 0 patients had a dose reduction compared to 63% of patients with score 1, 74% of those with score 2 and 100% of patients with score 3-5 (P=0.03); with regards to the adult comorbidity evaluation-27 score, 45% of patients had score 0-1 and 69% of patients with score 2-3 had a dose reduction. Of the 65 patients with Charlson score 0, 29% had at least one suspension of treatment (79% for hematologic and 21% for non-hematologic toxicity), compared to 46% of patients with score 1 (37% for hematologic and 69% for non-hematologic toxicity), 58% of patients with score 2 (36% for hematologic and 64% for non-hematologic toxicity) and 100% of patients with score 3 or 4 (all patients for both types of toxicity). High adult comorbidity index-27 scores identified patients at high risk of grade 3/4 hematologic toxicity. Forty-one patients (32.8%) experienced pleural effusion during treatment: the highest scores for both indices were associated with an increased risk of pleural effusions. ConclusionsIn elderly patients with chronic myeloid leukemia treated with dasatinib, the rate of drug reduction or suspension and the incidence of pleural effusions seem to be associated with the presence of comorbidities: stratification according to the Charlson index and adult comorbidity evaluation-27 score before dasatinib therapy may enable the identification of patients at risk of major toxicities.Key words: chronic myeloid leukemia, dasatinib, Charlson comorbidity index, adult comorbidity evaluation 27 (ACE-27).Citation: Breccia M, Latagliata R, Stagno F, Luciano L, Gozzini A, Castagnetti F, Fava C, Cavazzini F, Annunziata M, Russo Rossi A, Pregno P, Abruzzese E, Vigneri P, Rege-Cambrin G, Sica S, Pane F, Santini V, Specchia G, Rosti G, and Alimena G. Charlson comorbidity index and adult comorbidity evaluation-27 scores might predict treatment complia...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Charlson comorbidity index and adult comorbidity evaluation-27 scores might predict treatment compliance and development of pleural effusions in elderly patients with chronic myeloid leukemia treated with second-line dasatinib

Breccia¹,

Latagliata²,

Stagno³

et al. 2011

Haematologica

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“…The suggested mechanism is probably related to kinase inhibition: imatinib potently inhibits platelet-derived growth factor receptor-b which is expressed in pericytes and is involved in the regulation of angiogenesis. [10] Imatinib can also induce cardiotoxicity which can range from asymptomatic LV dysfunction to congestive heart failure. Hence, it should be ruled out in any patient who presents with breathlessness on imatinib therapy.…”

Section: Discussionmentioning

confidence: 99%

Imatinib-induced pleural effusion

Banka

Udwadia

2017

Journal of Postgraduate Medicine

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Imatinib is a tyrosine kinase inhibitor and has rarely been reported to cause pleural effusion. We report the case of an 88-year-old male, known case of gastrointestinal stromal tumor on treatment with imatinib, who presented with a 2-week history of cough and dyspnea. He was diagnosed to have a right-sided pleural effusion and thoracentesis of the fluid revealed an exudate with low adenosine deaminase and negative cytology. Withdrawal of the drug lead to resolution of symptoms. We report this case to highlight the side effect profile of imatinib and warn physicians regarding this potential adverse effect which may be mistaken for metastasis or infection.

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“…The incidence of pleural effusion ranged from 14% to 30% in the phase I trial, 25% in the START trials, and 14% in the CA180-034 study. [43] Porkka et al [44] reported a slight increase in the incidence of all grades of pleural effusion between 24 and 36 months of follow-up in the phase III CA180-034 study, but the occurrence of this adverse event did not influence the efficacy of the drug. Until now, none of the published studies have performed a complete analysis of concomitant diseases or medications associated with dasatinib-induced pleural effusion, but it has been reported that older age (>65 years) is the most important negative prognostic factor.…”

Section: Most Common Adverse Effects Of Dasatinibmentioning

confidence: 97%

Activity and Safety of Dasatinib as Second-Line Treatment or in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia Patients

Breccia

2011

BioDrugs

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Dasatinib is an oral dual tyrosine kinase inhibitor active against ABL1 and SRC family kinases. The US FDA approved it for the treatment of chronic myeloid leukemia (CML) patients in chronic, accelerated, or blastic phase with resistance or intolerance to imatinib therapy. Dasatinib is also indicated for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia who have become resistant to or intolerant of other treatments. The agent is now also approved for newly diagnosed chronic phase (CP) patients. This article reviews the pharmacokinetic and pharmacodynamic properties of dasatinib as well as clinical data limited to CP-CML patients. Four-year follow-up of a phase III dose-optimization trial confirmed that better progression-free survival (66%) and overall survival (82%) were obtained with a dose of 100 mg once daily (od) than with the standard 70 mg twice daily dosing (65% and 75%, respectively). The 100 mg od dosing schedule was also associated with the highest benefit-risk ratio for CP patients with resistant, intolerant, or suboptimal response. Recent results of a phase III trial in newly diagnosed patients demonstrated that dasatinib 100 mg od has superiority in terms of confirmed cytogenetic and molecular responses, with faster responses and high activity in high Sokal risk patients compared with standard-dose imatinib.

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Pleural/pericardic effusions during dasatinib treatment: incidence, management and risk factors associated to their development

Abstract: Literature evidences support the fact that with adequate management and monitoring of patients with predisposing factors, pleural effusions can be easily managed.

Cited by 25 publications

References 50 publications

Charlson comorbidity index and adult comorbidity evaluation-27 scores might predict treatment compliance and development of pleural effusions in elderly patients with chronic myeloid leukemia treated with second-line dasatinib

Charlson comorbidity index and adult comorbidity evaluation-27 scores might predict treatment compliance and development of pleural effusions in elderly patients with chronic myeloid leukemia treated with second-line dasatinib

Imatinib-induced pleural effusion

Activity and Safety of Dasatinib as Second-Line Treatment or in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia Patients

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