Pharmacokinetics of paclitaxel administered as a 3-hour or 96-hour infusion

Pharmacol Res. 1999 Jul;40(1):67-74. doi: 10.1006/phrs.1999.0477.

Abstract

Aim: To investigate the pharmacokinetics of paclitaxel (Paxene) administered to patients with advanced breast or ovarian cancer and to document safety and anti-tumour activity in this study population.

Patients and methods: Patients with advanced breast or ovarian cancer were accrued to two clinical studies. Paclitaxel (Paxene) was administered as a 3-h 175 mg m-2 or as a 96-h 140 mg m-2(105 mg m-2 in the presence of liver metastases) infusion. Patients not responding to the 3-h schedule were permitted to cross-over to the 96-h schedule. The data were compared to those of five patients who were previously treated with paclitaxel administered as Taxol (140 mg m-296-h infusion) at our Institute.

Results: Fourteen patients with breast cancer and five ovarian cancer patients were entered into this study. Seven patients received the 3-h regimen, and 12 were assigned to the 96-h schedule. Five patients originally treated with the 3-h schedule, crossed over to the 96-h arm. For the 3-h 175 mg m-2 dose, the area under the plasma concentration vs time curve (AUC) was (mean+/-SD) 16.9+/-4.8 h x micromol x l-1, whereas the AUCs were 5.5+/-1.2 and 4.3+/-0.9 h x micromol x l-1 for the 96-h 140 mg m-2 and 105 mg m-2 doses, respectively. The clearance of paclitaxel was independent of the dose in the 96-h group, indicating linear pharmacokinetics. Pharmacokinetics of Paxene (96-h 140 mg m-2) were not significantly different from the kinetics after Taxol (96-h 140 mg m-2) administration.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Female
  • Humans
  • Infusions, Intravenous
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Paclitaxel / pharmacokinetics*
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Phytogenic
  • Paclitaxel