Metabolism of the taxanes including nab-paclitaxel

Abstract

Introduction: The classical taxanes (paclitaxel, docetaxel), the newer taxane cabazitaxel and the nanoparticle-bound nab-paclitaxel are among the most widely used anticancer drugs. Despite years of research, the optimal dosing regimen (weekly vs 3-weekly) and optimal dose is still controversial, as is the value of pharmacological personalization of taxane dosing.

Areas covered: This review provides an overview of the pharmacological properties of the taxanes, including metabolism, pharmacokinetics–pharmacodynamics and aspects in the clinical use of taxanes. The latter includes the ongoing debate on the most active and safe regimen (paclitaxel, docetaxel, nab-paclitaxel), the recommended initial dose (cabazitaxel) and pharmacological dosing individualization.

Expert opinion: Taxanes share the characteristics of extensive hepatic metabolism and biliary excretion, the need for dose adaptation in patients with liver dysfunction, and substantial pharmacokinetic variability even after taking into account known covariates. Data from clinical studies suggest that optimal scheduling of the taxanes is dependent not only on the specific taxane compound, but also on the tumor type and line of treatment. Finally, treating oncologists should be aware of the substantial risk for drug–drug interactions that is a direct consequence of the complex hepatic metabolism of the taxanes.

Keywords:

• cabazitaxel
• docetaxel
• metabolism
• nab-paclitaxel
• paclitaxel
• pharmacokinetics
• taxanes

Declaration of interest

The author is study chair of clinical studies exploring the value of therapeutic drug monitoring of paclitaxel (CEPAC-TDH study, sponsored by Saladax Biomedical, Inc.) and cabazitaxel (CAINTA study, partly sponsored by Sanofi-Aventis). The author has no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

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