Dataset Information

Pharmacology of tyrosine kinase inhibitors in chronic myeloid leukemia; a clinician's perspective.

ABSTRACT:

Objective

In this review, we have summarized the pharmacokinetics, pharmacodynamics and adverse effects of imatinib, dasatinib, nilotinib, bosutinib, ponatinib and radotinib with focus on pharmacogenomic studies with clinical end points. We have discussed the key phase 3 trials of tyrosine kinase inhibitors (TKI) comparing with each other, treatment free remission (TFR) and selection of TKI. Upcoming concepts and related trials in the management of chronic myeloid leukemia (CML) along with future directions have been touched upon.

Evidence acquisition

PubMed, Embase, Google, Cochrane library and Medline were searched to identify relevant literature for the review. Clinicaltrial.gov was searched for upcoming data and trials.

Results

There are lot of gap in pharmacokinetics and pharmacodynamics of TKI. Imatinib appears to be the safest TKI. Newer TKI's achieve better achievement of therapeutic milestones, deeper molecular response and less chances of progression of CML compared to imatinib. Newer TKI appears to be better choice for achieving TFR. When the objective is survival, imatinib is still the TKI of choice. Primary prophylaxis with antiplatelet drugs for TKI having cardiovascular and thromboembolic side effects should be considered.

Conclusion

Pharmacogenetic data of TKI is still immature to guide in therapeutic decision making in clinical practice. There is need for further research in pharmacology and pharmacogenomics of newer TKI's. Randomized controlled trials are required to decide the optimum TKI for TFR. Safe and effective TKI for targeting T315I mutation, CML accelerated phase and blast crisis are an active area of research.

SUBMITTER: Pushpam D

PROVIDER: S-EPMC7214547 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Pharmacology of tyrosine kinase inhibitors in chronic myeloid leukemia; a clinician's perspective.

Pushpam Deepam D Bakhshi Sameer S

Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences 20200103 1

<h4>Objective</h4>In this review, we have summarized the pharmacokinetics, pharmacodynamics and adverse effects of imatinib, dasatinib, nilotinib, bosutinib, ponatinib and radotinib with focus on pharmacogenomic studies with clinical end points. We have discussed the key phase 3 trials of tyrosine kinase inhibitors (TKI) comparing with each other, treatment free remission (TFR) and selection of TKI. Upcoming concepts and related trials in the management of chronic myeloid leukemia (CML) along wi ...[more]

PMID: 31900888

Similar Datasets

Project description:IntroductionChronic myeloid leukemia (CML) is a chronic disease with treatment-free remission (TFR) increasingly regarded as a feasible goal of treatment. However, various factors may influence adherence to international guidelines for CML management. This study aimed to compare the reporting of care between patients with CML and their treating doctors.MethodsParallel patient and physician online surveys were conducted between September 22, 2021, and March 15, 2022, which focused on the perceptions of 1882 adult patients with CML and 305 physicians regarding tyrosine kinase inhibitor (TKI) treatment options, monitoring and toxicities, TFR, and challenges faced.ResultsAmong the enrolled patients, 69.9% received first-line imatinib treatment, 18.6% received nilotinib, and 4.7% received dasatinib. Among the patients treated with imatinib, 36.7% switched to other TKIs due to imatinib resistance/intolerance (71.1%), exploration of more potent TKIs to achieve TFR (8.9%), and treating physicians' recommendation (14.0%), with a median duration of initial treatment of 14 months [interquartile range (IQR) 6-36]. Most (91.8%) physicians agreed that the breakpoint cluster region-Abelson 1 (BCR::ABL1) transcript level should be assessed every 3 months, but only 42.7% of individuals committed to 3-monthly testing and only 17.8% strictly followed their treating physicians' recommendation. Half of the patients aimed for TFR; however, just 45.2% of physicians considered TFR as one of the top three goals for their patients. The major concern in obtaining TFR was patients' adherence. Fatigue was often distressing for patients with TKIs, while physicians were more concerned about platelet and neutrophil counts. A total of 12% and 20.8% of patients reported moderate/severe anxiety and depression, respectively, while only 53.7% of physicians had concerns about their patients' mental health. During the coronavirus disease 2019 (COVID-19) pandemic, 69.2% of patients reported a reduction in their income. Among these patients, 61.8% maintained their current treatment, while 7.3% switched to cheaper alternatives or discontinued treatment, with over 80% of these patients belonging to the low-income group.ConclusionsOvercoming challenges in patient-physician communication and treatment access is key to improving disease management and quality of life, especially for patients with low income.Trial registrationClinicalTrials.gov identifier NCT05092048.

Dataset Information

Pharmacology of tyrosine kinase inhibitors in chronic myeloid leukemia; a clinician's perspective.

Objective

Evidence acquisition

Results

Conclusion

Publications

Pharmacology of tyrosine kinase inhibitors in chronic myeloid leukemia; a clinician's perspective.

Similar Datasets

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