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Therapeutic Drug Monitoring of Oral Anti-Hormonal Drugs in Oncology
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Journal Article
Therapeutic Drug Monitoring of Oral Anti-Hormonal Drugs in Oncology
2019
Overview
Oral anti-hormonal drugs are essential in the treatment of breast and prostate cancer. It is well known that the interpatient variability in pharmacokinetic exposure is high for these agents and exposure–response relationships exist for many oral anti-hormonal drugs. Yet, they are still administered at fixed doses. This could lead to underdosing and thus suboptimal efficacy in some patients, while other patients could be overdosed resulting in unnecessary side effects. Therapeutic drug monitoring (TDM), individualized dosing based on measured blood concentrations of the drug, could therefore be a valid option to further optimize treatment. In this review, we provide an overview of relevant clinical pharmacokinetic and pharmacodynamic characteristics of oral anti-hormonal drugs in oncology and translate these into practical guidelines for TDM. For some agents, TDM targets are not well established yet and as a reference the median pharmacokinetic exposure could be targeted (exemestane: minimum plasma concentration (
C
min
) 4.1 ng/mL and enzalutamide:
C
min
11.4 mg/L). However, for most drugs, exposure–efficacy analyses could be translated into specific targets (abiraterone:
C
min
8.4 ng/mL, anastrozole:
C
min
34.2 ng/mL, and letrozole:
C
min
85.6 ng/mL). Moreover, prospective clinical trials have shown TDM to be feasible for tamoxifen, for which the exposure–efficacy threshold of its active metabolite endoxifen is 5.97 ng/mL. Based on the available data, we therefore conclude that individualized dosing based on drug concentrations is feasible and promising for oral anti-hormonal drugs and should be developed further and implemented into clinical practice.
Publisher
Springer International Publishing,Springer Nature B.V
Subject
/ Antineoplastic Agents, Hormonal - administration & dosage
/ Antineoplastic Agents, Hormonal - blood
/ Antineoplastic Agents, Hormonal - pharmacokinetics
/ Aromatase Inhibitors - blood
/ Breast Neoplasms - drug therapy
/ Estrogen Receptor Modulators - blood
/ Estrogen Receptor Modulators - metabolism
/ Fasting
/ Female
/ Food
/ Humans
/ Male
/ Meals
/ Medicine
/ Oncology
/ Prostatic Neoplasms - drug therapy
/ Women
