1,721,300 research outputs found
Are there new clinical parameters useful to predict response in chronic myeloid leukemia in the imatinib era?
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Bringing prognostic scores for chronic myeloid leukemia patients up to date
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Pleural/pericardic effusions during dasatinib treatment: incidence, management and risk factors associated to their development
No full textImportance of the field: Despite the beneficial effect of imatinib treatment in chronic myeloid leukemia patients, some patients develop resistance and/or intolerance and need a switch to second-generation tyrosine kinase inhibitors. Dasatinib is indicated for chronic myeloid leukemia patients with resistance or intolerance to imatinib; it has 325-fold increase potency compared to imatinib and is active in mutated and unmutated resistant patients. Pleural/pericardic effusions are frequent complications during treatment with dasatinib, and usually are reported to require dose reduction or drug discontinuation. Changing the dasatinib regimen from 70 mg twice daily to 100 mg once daily reduces the risk of pleural effusions. Area covered in this review: In this article, we review the incidence of the phenomenon observed in different dasatinib trials (Phase I - III) and the currently suggested management. We also describe the identified pathogenetic mechanisms related to the development and discuss the associated risk factors. What the reader will gain: The aim of this paper is to provide healthcare professionals with clear guidance on the management of pleural effusions associated with dasatinib treatment. Recommendations are based on the published data and clinical experience from a number of different centers. Take home message: Literature evidences support the fact that with adequate management and monitoring of patients with predisposing factors, pleural effusions can be easily managed
The current role of high-dose imatinib in chronic myeloid leukemia patients, newly diagnosed or resistant to standard dose
No full textIntroduction: The majority of patients affected by chronic myeloid leukemia (CML) are expected to obtain a favorable outcome with standard-dose imatinib. However, a third of patients do not achieve the desired effect and must be considered resistant. One of the early strategies to overcome initial resistance was the use of high doses (600 - 800 mg) of imatinib: before the advent of second-generation tyrosine kinase inhibitors, some standard-dose-resistant patients gained benefits from the use of dose-escalation imatinib. Intensification with higher doses of the drug was used in newly diagnosed patients with the aim to improve cytogenetic and molecular responses. Areas covered: In this article, the authors review data of several trials testing high-dose imatinib after resistance to standard dose. Literature about high-dose imatinib used front-line as single treatment or with different combinations is also examined. A literature search for relevant studies was undertaken mainly in PubMed or through published conference abstracts. The aim of this review is to summarize the efficacy and safety of this option either as front-line or as a rescue therapy in chronic-phase CML patients and to discuss the future role of this treatment modality. Expert opinion: Literature evidence supports the fact that high-dose imatinib can induce sustained responses in a subset of patients with cytogenetic failure or acquired resistance, but it seems less effective in patients with haematological failure or in molecular suboptimal responders. In newly diagnosed patients, high-dose imatinib produced increased response rates, which in some instances were not significant compared with standard dose
Nilotinib and dasatinib first-line: Are we ready for imatinib replacement?
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The significance of early, major and stable molecular responses in chronic myeloid leukemia in the imatinib era
No full textTyrosine kinase inhibitors (TKI) have dramatically changed the management and the outcome of chronic myeloid leukemia (CML) patients. Imatinib is recognized as gold standard first-line therapy and impressive clinical and cytogenetic responses are obtained in the majority of chronic phase patients treated with this drug. Quantitative polymerase chain reaction (RQ-PCR) tool is used to monitor molecular residual disease, but practical issues are associated to measurement of molecular responses. Several evidences have now proved that molecular responses have prognostic significance: patients who achieve early molecular response are more likely to obtain durable cytogenetic response and to present less rate of disease progression. While some reports indicated that achieving major molecular response (MMR) represents the most important endpoint associated to best outcome, some other reports indicated that achievement of MMR does not improve the greatest clinical benefit brought by complete cytogenetic response. In this review, we discuss on the role of molecular monitoring, the significance of early response and its correlation with outcome, the significance of major and complete molecular response, the emphasized value of a stable molecular response, the early identification of resistance presenting with increased molecular level. (C) 2010 Elsevier Ireland Ltd. All rights reserved
Activity and safety of dasatinib as second-line treatment or in newly diagnosed chronic phase chronic myeloid leukemia patients
No full textDasatinib 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 100mg once daily (od) than with the standard 70mg twice daily dosing (65 and 75, respectively). The 100mg 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 100mg 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. © 2011 Adis Data Information BV. All rights reserved
Adherence to treatment is a complex and multifaceted issue that can substantially alter the outcome of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors
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Progressive arterial occlusive disease (PAOD) and pulmonary arterial hypertension (PAH) as new adverse events of second generation TKIs in CML treatment: Who's afraid of the big bad wolf?
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Imatinib treatment in chronic myelogenous leukemia What have we learned so far?
No full textImatinib mesylate is currently the standard therapy for chronic myelogenous leukemia patients Despite the remarkable results achieved with imatinib the emergence of resistance to this drug has become a significant problem Actually two other second-generation tyrosine kinase inhibitors have been used for resistant/intolerant patients to imatinib With the availability of oral tyrosine kinase inhibitors for the treatment of chronic myelogenous leukemia questions relating to adherence to prescribed therapy have become an important issue It has been demonstrated that the effectiveness, of the treatment with imatinib requires high compliance to the prescribed dose of the drug for an indefinite period of time whereas reduced adherence to therapy has been associated with delay in achieving cytogenetic or molecular response and/or possible development of resistance The aim of this review is to discuss the Importance of adherence and the possible tools that we have to measure it to improve our knowledge on possible underlying causes of non-adherence and the Impact of non-adherence on hospitalization risk and healthcare cost through a systematic review of the data published to date (C) 2010 Elsevier Ireland Ltd All rights reserve
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