Pharmacokinetic analysis of two different docetaxel dose levels in patients with non-small cell lung cancer treated with docetaxel as monotherapy or with concurrent radiotherapy

BMC Cancer. 2007 Oct 23:7:197. doi: 10.1186/1471-2407-7-197.

Abstract

Background: Previous pharmacokinetic studies with docetaxel have mostly used 3-weekly (75 mg/m2 and 100 mg/m2) or weekly regimens (35-40 mg/m2). The pharmacokinetics and radiosensitizing efficacy of weekly 20 mg/m2 docetaxel, has however not been well characterized. We examined the pharmacokinetics of weekly docetaxel when administered with concurrent radiotherapy and compared the results with a 3-weekly 100 mg/m2 regimen.

Methods: Thirty-four patients with non small cell lung cancer (NSCLC) were included in this study, 19 receiving 100 mg/m2 docetaxel 3-weekly as single therapy, and 15 receiving 20 mg/m2 docetaxel weekly with concurrent radiotherapy. A newly developed HPLC method was used for measuring docetaxel levels, capable of quantifying docetaxel in plasma down to the nanomolar level.

Results: The HPLC method showed detectable concentrations of docetaxel in plasma even after 72 hours. In the present study we have demonstrated that median docetaxel plasma levels of 3 nM can be obtained 72 hours after a dose of 20 mg/m2.

Conclusion: The pharmacokinetics of docetaxel is characterized by great inter-individual variability and at some time points plasma concentrations for 20 mg/m2 and 100 mg/m2 docetaxel were overlapping. Extrapolation of these results indicates that radio sensitizing docetaxel concentrations may be present for as long as 1 week, thus supporting the use of 20 mg/m2 weekly docetaxel.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Antineoplastic Agents* / administration & dosage
  • Antineoplastic Agents* / blood
  • Antineoplastic Agents* / pharmacokinetics
  • Area Under Curve
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / radiotherapy
  • Chromatography, High Pressure Liquid
  • Combined Modality Therapy
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / radiotherapy
  • Male
  • Middle Aged
  • Orosomucoid / analysis
  • Radiotherapy
  • Reproducibility of Results
  • Taxoids* / administration & dosage
  • Taxoids* / blood
  • Taxoids* / pharmacokinetics

Substances

  • Antineoplastic Agents
  • Orosomucoid
  • Taxoids
  • Docetaxel