Plasma and tissue pharmacokinetics of epirubicin and Paclitaxel in patients receiving neoadjuvant chemotherapy for locally advanced primary breast cancer

Clin Pharmacol Ther. 2007 May;81(5):659-68. doi: 10.1038/sj.clpt.6100067. Epub 2007 Feb 14.

Abstract

The objective of the study was to assess individual distribution of antineoplastic drugs into the tumor. Twelve advanced-stage primary breast cancer patients with neoadjuvant epirubicin+paclitaxel chemotherapy were studied. Plasma concentrations of epirubicin and paclitaxel were monitored for 24 h. Epirubicin concentrations in subcutaneous and tumor tissues were measured using microdialysis up to 12 h postdose. Epirubicin concentrations were described by a compartmental population pharmacokinetic model (NONMEM). Noncompartmental analysis was used for paclitaxel. Plasma pharmacokinetics corresponded to published data. Mean epirubicin exposure in the tumor and in subcutaneous tissue was very similar, but tissue Cmax and area under the curve values reached only (means) 1% and 11%, respectively, of plasma values. Epirubicin doses were significantly correlated to tumor exposure irrespective of body surface area. There is no specific barrier for epirubicin to reach primary breast cancer tumors.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adipose Tissue / metabolism
  • Antibiotics, Antineoplastic / pharmacokinetics*
  • Antibiotics, Antineoplastic / therapeutic use
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Area Under Curve
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Epirubicin / pharmacokinetics*
  • Epirubicin / therapeutic use
  • Female
  • Humans
  • Microdialysis
  • Paclitaxel / pharmacokinetics*
  • Paclitaxel / therapeutic use

Substances

  • Antibiotics, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Epirubicin
  • Paclitaxel