Treatment regimens of classical and newer taxanes

Cancer Chemother Pharmacol. 2016 Feb;77(2):221-33. doi: 10.1007/s00280-015-2893-6. Epub 2015 Nov 20.

Abstract

The classical taxanes (paclitaxel, docetaxel), the newer taxane cabazitaxel and the nanoparticle-bound nab-paclitaxel are among the most widely used anticancer drugs. The taxanes share the characteristics of extensive hepatic metabolism and biliary excretion, the need for dose adaptation in patients with liver dysfunction, and a 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. Still, the optimal dosing regimen (weekly vs 3 weekly) and optimal dose of the taxanes are controversial, as is the value of pharmacological personalization of taxane dosing. In this article, an overview is given on 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, the recommended initial dose and the issue of therapeutic drug dosing.

Keywords: Cabazitaxel; Docetaxel; Nab-paclitaxel; Paclitaxel; Pharmacokinetics; Therapeutic drug monitoring.

Publication types

  • Review

MeSH terms

  • Albumins / metabolism
  • Albumins / pharmacokinetics
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacokinetics
  • Chemical and Drug Induced Liver Injury* / etiology
  • Chemical and Drug Induced Liver Injury* / metabolism
  • Chemical and Drug Induced Liver Injury* / prevention & control
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Neoplasms / classification
  • Neoplasms / drug therapy*
  • Paclitaxel / metabolism
  • Paclitaxel / pharmacokinetics
  • Taxoids* / classification
  • Taxoids* / metabolism
  • Taxoids* / pharmacokinetics
  • Treatment Outcome
  • Tubulin Modulators / metabolism
  • Tubulin Modulators / pharmacokinetics

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Antineoplastic Agents
  • Taxoids
  • Tubulin Modulators
  • Docetaxel
  • cabazitaxel
  • Paclitaxel