Therapeutic Drug Monitoring of Protein Kinase Inhibitors in Breast Cancer Patients

Roušarová, Jaroslava; Šíma, Martin; Slanař, Ondřej

doi:10.14712/23362936.2021.22

Cited by 6 publications

(7 citation statements)

References 49 publications

(77 reference statements)

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“…10 Target C min values of abemaciclib (200–210 ng/mL) and ribociclib (711 ng/mL) for TDM have also been proposed but require confirmation in prospective studies. 11 In addition to TDM, a bioanalytical assay for CDK4/6 inhibitors would also be useful for pharmacogenetic studies. As reported most recently for palbociclib, polymorphisms could be associated with the pharmacokinetics and/or pharmacodynamics of CDK4/6 inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a Quantitative LC-MS/MS Method for CDK4/6 Inhibitors Palbociclib, Ribociclib, Abemaciclib, and Abemaciclib-M2 in Human Plasma

Burke

Kamal

Goey

2023

Therapeutic Drug Monitoring

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Section: Introductionmentioning

confidence: 99%

Development and Validation of a Quantitative LC-MS/MS Method for CDK4/6 Inhibitors Palbociclib, Ribociclib, Abemaciclib, and Abemaciclib-M2 in Human Plasma

Burke

Kamal

Goey

2023

Therapeutic Drug Monitoring

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“…In a review, Falkowski and Woillard (2019) reported that a trough concentration higher than 20 ng/ml could be proposed as a threshold to indicate an increased risk of overall severe toxicity. Furthermore, Roušarová et al (2021) reported that a trough concentration between 10 and 20 ng/ml was a promising therapeutic drug monitoring target for everolimus in breast cancer treatment, in a review of therapeutic drug monitoring of protein kinase inhibitors in patients with breast cancer. The findings from these reports support our study’s findings.…”

Section: Discussionmentioning

confidence: 99%

Everolimus pharmacokinetics and exposure-response relationship in Japanese patients with advanced breast cancer

et al. 2022

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Background: Everolimus is one of the key drugs for the treatment of advanced breast cancer. The optimal target concentration range for everolimus therapy in patients with breast cancer has not yet been established. This study aimed to characterize everolimus pharmacokinetics (PK) and determine the relationship between blood concentration and efficacy as well as adverse events in patients with breast cancer.Methods: This was a prospective, observational PK study. Patients receiving everolimus between November 2015 and November 2018 at our hospital were enrolled in this study. The whole blood samples for the everolimus assay were collected at least two weeks after initiation of treatment or the last everolimus dose change. PK parameters were estimated using Bayesian analysis. Statistical differences in everolimus trough concentrations between patient cohorts were assessed using the Mann-Whitney test. Progression-free survival was assessed using the Kaplan-Meier method and the log-rank test.Results: Eighteen patients were enrolled in the study. The median follow-up period was 35 months. The most frequently observed adverse event was stomatitis (all grade 94%). There was high inter-individual variation in PK parameters such as clearance [range: 5.1-21.3 L/h/70 kg and co-efficient of variation (CV): 38.5%] and volume of distribution of the central compartment (range: 9.9-103.6 L/70 kg and CV: 57.8%). The trough concentrations at doselimiting toxicities were significantly higher than trough concentrations in the absence of these toxicities (p = 0.0058). Progression-free survival was significantly longer in the 10-20 ng/ml group than in the other groups (p = 0.0078). Conclusion:This study characterized the everolimus PK parameters in Japanese patients with breast cancer. High everolimus exposure was found to be associated with poor tolerability. Based on our data, trough

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“…39 A relationship between exposure and response and/or safety has been established and therapeutic targets have already been reported for some drugs. 40,41 Systemic physiologic changes are very dynamic in AKI patients. Drug clearance and distribution vary in the short term (some hours and days) and it is difficult to practically quantify the glomerular filtration rate (GFR) 42 as well as liver metabolism.…”

Section: Impact Of Kidney Pathologies On Tki Pharmacokineticsmentioning

confidence: 99%

Pharmacology of Tyrosine Kinase Inhibitors

Hulin,

Gelé,

Fenioux

et al. 2023

CJASN

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Tyrosine kinase inhibitors (TKI) have introduced a significant advancement in cancer management. These compounds are administered orally, and their absorption holds a pivotal role in determining their variable efficacy. They exhibit extensive distribution within the body, binding strongly to both plasma and tissue proteins. Often reliant on efflux and influx transporters, TKI undergo primary metabolism by intestinal and hepatic cytochrome P450 enzymes, with non-kidney clearance being predominant. Due to their limited therapeutic window, many TKI display considerable intra- and interindividual variability. This review offers a comprehensive analysis of the clinical pharmacokinetics of TKI, detailing their interactions with drug transporters and metabolic enzymes, while discussing potential clinical implications. The prevalence of kidney conditions, such as acute kidney injury (AKI) and chronic kidney disease (CKD), among cancer patients is explored in terms of their impact on TKI pharmacokinetics. Lastly, the potential nephrotoxicity associated with TKI is also examined.

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Therapeutic Drug Monitoring of Protein Kinase Inhibitors in Breast Cancer Patients

Cited by 6 publications

References 49 publications

Development and Validation of a Quantitative LC-MS/MS Method for CDK4/6 Inhibitors Palbociclib, Ribociclib, Abemaciclib, and Abemaciclib-M2 in Human Plasma

Development and Validation of a Quantitative LC-MS/MS Method for CDK4/6 Inhibitors Palbociclib, Ribociclib, Abemaciclib, and Abemaciclib-M2 in Human Plasma

Everolimus pharmacokinetics and exposure-response relationship in Japanese patients with advanced breast cancer

Pharmacology of Tyrosine Kinase Inhibitors

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