Pharmacogenetics, Enzyme Probes and Therapeutic drug Monitoring as Potential Tools for Individualizing Taxane Therapy

Abstract

The taxanes are a class of chemotherapeutic agents that are widely used in the treatment of various solid tumors. Although taxanes are highly effective in cancer treatment, their use is associated with serious complications attributable to large interindividual variability in pharmacokinetics and a narrow therapeutic window. Unpredictable toxicity occurrence necessitates close patient monitoring while on therapy and adverse effects frequently require decreasing, delaying or even discontinuing taxane treatment. Currently, taxane dosing is based primarily on body surface area, ignoring other factors that are known to dictate variability in pharmacokinetics or outcome. This article discusses three potential strategies for individualizing taxane treatment based on patient information that can be collected before or during care. The clinical implementation of pharmacogenetics, enzyme probes or therapeutic drug monitoring could enable clinicians to personalize taxane treatment to enhance efficacy and/or limit toxicity.

KEYWORDS::

• docetaxel
• enzyme probe
• paclitaxel
• personalized medicine
• pharmacogenetics
• therapeutic drug monitoring

Financial & competing interests disclosure

This work was supported in part by NIH grants UL1 RR025747 and P01CA142538 and the UNC University Cancer Research Fund. DL Hertz is an AFPE fellow and SD Krens received a student grant from the Dutch Cancer Society and the Royal Dutch Pharmacists Association. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported in part by NIH grants UL1 RR025747 and P01CA142538 and the UNC University Cancer Research Fund. DL Hertz is an AFPE fellow and SD Krens received a student grant from the Dutch Cancer Society and the Royal Dutch Pharmacists Association. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.