Abstract
Imatinib mesylate (IM) is the standard treatment for advanced, metastatic gastrointestinal stromal tumors (GISTs) and chronic myeloid leukemia (CML) with a fixed daily standard dosage via the oral route. Interindividual and intraindividual variability in plasma concentrations have been closely linked to the efficacy of IM therapy. Therefore, this review identifies and describes the key factors influencing the plasma concentration of IM in patients with GISTs and CML. We used the following keywords to search the PubMed, EMBASE, Ovid, Wangfang, and CNKI databases to identify published reports: IM, plasma concentration, GISTs, CML, drug combination/interaction, pathology, and genotype/genetic polymorphism, either alone or in combination. This literature review revealed that only 10 countries have reported the mean concentrations of IM in GISTs or CML patients and the clinical outcomes in different ethnic groups and populations. There were totally 24 different gene polymorphisms, which were examined for any potential influence on the steady-state plasma concentration of IM. As a result, some genotype locus made discrepant conclusion. Herein, the more sample capacity, multicenter, long-term study was worthy to carry out. Eleven reports were enumerated on clinical drug interactions with IM, while there is not sufficient information on the pharmacokinetic parameters altered by drug combinations with IM that could help in investigating the actual drug interactions. The drug interaction with IM should be paid more attention in the future research.
Highlights
For the last 15 years, imatinib mesylate (IM) has been the first line of treatment for advanced, metastatic gastrointestinal stromal tumors (GISTs) (Rutkowski et al, 2020) and has been approved as therapy for Philadelphia chromosome-positive chronic myeloid leukemia (CML) (Markovic et al, 2020) via the oral route (Banegas et al, 2019)
A latest review (Buclin et al, 2020) summarized some standard steps of TDM for some specific drug using Imatinib mesylate (IM) as the example, that is, i) judging whether IM is a candidate to TDM, ii) thinking about the normal range for plasma concentration of IM, iii) defining what is the effective target for the concentration of IM, iv) reflecting on how to adjust the dosage of IM close to target concentration, and v) summarizing evidence supporting the usefulness of TDM for IM
Based on our literature review, we found that insufficient attention has been directed to drug interactions with IM in GISTs or CML patients
Summary
For the last 15 years, imatinib mesylate (IM) has been the first line of treatment for advanced, metastatic gastrointestinal stromal tumors (GISTs) (Rutkowski et al, 2020) and has been approved as therapy for Philadelphia chromosome-positive chronic myeloid leukemia (CML) (Markovic et al, 2020) via the oral route (Banegas et al, 2019). Interpatient differences in therapeutic response may occur partly because of pharmacokinetic (PK) variability, which has been estimated to be ∼60 and 71% in IM steady-state trough concentrations in patients with GISTs or CML, respectively (Gandia et al, 2013; Zhuang et al, 2018). The main side effects of IM in patients with GISTs, such as myelosuppression and periocular edema, have been observed in ∼50% of the patients (Ondecker et al, 2018) Most of these side effects have been classified as moderate, grade-1, or grade-2 adverse events, according to the Common Terminology Criteria for Adverse Events, the quality of life could be adversely affected to a significant degree by physical and psychosocial discomfort (Abu-Amna et al, 2016).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
