scholarly journals Pharmacokinetic Targets for Therapeutic Drug Monitoring of Small Molecule Kinase Inhibitors in Pediatric Oncology

2020 ◽  
Vol 108 (3) ◽  
pp. 494-505 ◽  
Author(s):  
Julie M. Janssen ◽  
Thomas P. C. Dorlo ◽  
Neeltje Steeghs ◽  
Jos H. Beijnen ◽  
Lidwien M. Hanff ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Small Molecule ◽  
Pediatric Oncology ◽  
Drug Monitoring ◽  
Kinase Inhibitors ◽  
Therapeutic Drug

scholarly journals Feasibility of Extrapolating Randomly Taken Plasma Samples to Trough Levels for Therapeutic Drug Monitoring Purposes of Small Molecule Kinase Inhibitors

2021 ◽  
Vol 14 (2) ◽  
pp. 119
Author(s):  
Ruben A. G. van Eerden ◽  
Esther Oomen-de Hoop ◽  
Aad Noordam ◽  
Ron H. J. Mathijssen ◽  
Stijn L. W. Koolen
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Small Molecule ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Half Life ◽  
Kinase Inhibitors ◽  
Therapeutic Drug ◽  
Blood Samples ◽  
Elimination Half ◽  
Trough Levels

Small molecule kinase inhibitors (SMKIs) are widely used in oncology. Therapeutic drug monitoring (TDM) for SMKIs could reduce underexposure or overexposure. However, logistical issues such as timing of blood withdrawals hamper its implementation into clinical practice. Extrapolating a random concentration to a trough concentration using the elimination half-life could be a simple and easy way to overcome this problem. In our study plasma concentrations observed during 24 h blood sampling were used for extrapolation to trough levels. The objective was to demonstrate that extrapolation of randomly taken blood samples will lead to equivalent estimated trough samples compared to measured Cmin values. In total 2241 blood samples were analyzed. The estimated Ctrough levels of afatinib and sunitinib fulfilled the equivalence criteria if the samples were drawn after Tmax. The calculated Ctrough levels of erlotinib, imatinib and sorafenib met the equivalence criteria if they were taken, respectively, 12 h, 3 h and 10 h after drug intake. For regorafenib extrapolation was not feasible. In conclusion, extrapolation of randomly taken drug concentrations to a trough concentration using the mean elimination half-life is feasible for multiple SMKIs. Therefore, this simple method could positively contribute to the implementation of TDM in oncology.

scholarly journals Therapeutic drug monitoring of small molecule kinase inhibitors in oncology in a real-world cohort study: does age matter?

2018 ◽  
Vol 84 (12) ◽  
pp. 2770-2778 ◽  
Author(s):  
Marie-Rose B.S. Crombag ◽  
Jacobine G.C. van Doremalen ◽  
Julie M. Janssen ◽  
Hilde Rosing ◽  
Jan H.M. Schellens ◽  
...  
Keyword(s):  
Cohort Study ◽  
Therapeutic Drug Monitoring ◽  
Small Molecule ◽  
Real World ◽  
Drug Monitoring ◽  
Kinase Inhibitors ◽  
Therapeutic Drug

scholarly journals Therapeutic Drug Monitoring of Protein Kinase Inhibitors in Breast Cancer Patients

2021 ◽  
Vol 122 (4) ◽  
pp. 243-256
Author(s):  
Jaroslava Roušarová ◽  
Martin Šíma ◽  
Ondřej Slanař
Keyword(s):  
Breast Cancer ◽  
Protein Kinase ◽  
Therapeutic Drug Monitoring ◽  
Cancer Treatment ◽  
Drug Monitoring ◽  
Kinase Inhibitors ◽  
Breast Cancer Treatment ◽  
Protein Kinase Inhibitors ◽  
Therapeutic Drug ◽  
Exposure Response

Protein kinase inhibitors (PKIs) represent up-to-date therapeutic approach in breast cancer treatment. Although cancer is a rapidly progressive disease, many substances, including PKIs, are usually used at fixed doses without regard to each patient’s individuality. Therapeutic drug monitoring (TDM) is a tool that allows individualization of therapy based on drug plasma levels. For TDM conduct, exposure-response relationships of drug substances are required. The pharmacokinetic data and exposure-response evidence supporting the use of TDM for 6 PKIs used in breast cancer treatment, one of the most common female tumour diseases, are discussed in this review.

scholarly journals The Right Dose: From Phase I to Clinical Practice

2021 ◽  
pp. 92-106
Author(s):  
Stefanie L. Groenland ◽  
Mark J. Ratain ◽  
Lisa S. Chen ◽  
Varsha Gandhi
Keyword(s):  
Clinical Practice ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Kinase Inhibitors ◽  
Optimal Dose ◽  
Therapeutic Drug ◽  
Full Potential ◽  
Drug Dosing ◽  
Anticancer Treatment ◽  
The Right

To realize the full potential of promising new anticancer drugs, it is of paramount importance to administer them at the right dose. The aim of this educational article is to provide several opportunities to optimize anticancer drug dosing, focusing on oral targeted therapies. First, therapeutic drug monitoring can optimize exposure in individual patients, if the optimal concentration is known. This approach is of particular interest in regard to oral kinase inhibitors with high interindividual pharmacokinetic variability. If exposure is related to response, then therapeutic drug monitoring is potentially feasible, although the clinical utility of this approach has not yet been established. Other approaches to reduce variability include administration of more frequent, smaller doses and administration under optimal prandial conditions. However, for many drugs, the labeled dose has not been demonstrated to be the optimal dose; for such agents, the vast majority of patients may be receiving excessive doses, which results in excessive toxicity. Furthermore, administration of lower off-label doses may reduce both medical and financial toxicity. These strategies should be applied from registration studies to clinical practice, with the goal of better optimizing anticancer treatment.

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