Pharmacokinetics and toxicity of weekly docetaxel in older patients

Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6100-5. doi: 10.1158/1078-0432.CCR-06-0200.

Abstract

Purpose: To evaluate the pharmacokinetics of weekly docetaxel in a cohort of older patients with metastatic cancer and to explore the relationship of pharmacokinetic variables, Erythromycin Breath Test results, age, geriatric assessment variables, and toxicity to therapy.

Experimental design: Twenty patients ages > or = 65 years with metastatic breast, prostate, or lung cancer entered an Institutional Review Board-approved protocol to evaluate the pharmacokinetics of weekly docetaxel administered at 35 mg/m2 i.v. for 3 weeks followed by a 1-week break. The Erythromycin Breath Test and geriatric assessment were done before the first dose. Blood samples were collected for pharmacokinetic analysis with the first dose of docetaxel.

Results: Of the 20 patients who entered the study, 19 were evaluable. There were no age-related differences in the pharmacokinetics of weekly docetaxel. Fifty-eight percent (11 of 19) experienced grade > or = 3 toxicity: 16% (3 of 19) grade > or = 3 hematologic toxicity, and 53% (10 of 19) grade > or = 3 nonhematologic toxicity. There was an association between the Erythromycin Breath Test results and docetaxel pharmacokinetic variables; however, there was no association between Erythromycin Breath Test results or docetaxel pharmacokinetics with frequency of grade > or = 3 toxicity.

Conclusions: Despite no statistically significant age-related differences in weekly docetaxel pharmacokinetics, over half of these older patients experienced a grade > or = 3 toxicity at the 35 mg/m2 starting dose. We advocate a starting dose of 26 mg/m2 on this weekly schedule and dose escalating if no toxicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / drug effects*
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Antineoplastic Agents, Phytogenic / toxicity
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Docetaxel
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Neoplasm Metastasis
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Taxoids / pharmacokinetics*
  • Taxoids / toxicity*

Substances

  • Antineoplastic Agents, Phytogenic
  • Taxoids
  • Docetaxel