Comparative Pharmacokinetics of Weekly and Every-Three-Weeks Docetaxel

Sharyn D. Baker, Ming Zhao, Carlton K Lee, Jaap Verweij, Yelena Zabelina, Julie Brahmer, Antonio C Wolff, Alex Sparreboom, Michael A Carducci

Research output: Contribution to journalArticle

Abstract

Purpose: Weekly administration of docetaxel has demonstrated comparable efficacy together with a distinct toxicity profile with reduced myelosuppression, although pharmacokinetic data with weekly regimens are lacking. The comparative pharmacokinetics of docetaxel during weekly and once every 3 weeks (3-weekly) administration schedules were evaluated. Experimental Design: Forty-six patients received weekly docetaxel (35 mg/m2) as a 30-min infusion alone (n = 8) or in combination with irinotecan (n = 12), or in 3-weekly regimens, as a 1-h infusion at 60 mg/m2 with doxorubicin (n = 10), 75 mg/m2 alone (n = 9), or 100 mg/m2 alone (n = 7). Serial blood samples were obtained immediately before and up to 21 days after the infusion. Plasma concentrations were measured by liquid chromatography-mass spectrometry and analyzed by compartmental modeling. Results: Mean ± SD docetaxel clearance values were similar with weekly and 3-weekly schedules (25. 2 ± 7.7 versus 23.7 ± 7.9 liter/h/m2); half-lives were also similar with both schedules of administration (16.5 ± 11.2 versus 17.6 ± 7.4 h). With extended plasma sampling beyond 24 h post-infusion, docetaxel clearance was 18% lower and the terminal half-life was 5-fold longer. At 35 mg/m2, the mean ± SD docetaxel concentration on day 8 was 0.00088 ± 0.00041 μg/ml (1.08 ± 0.51 nM) at 75 mg/m 2, concentrations on day 8, 15, and 22 were 0.0014 ± 0.00043 μg/ml (1.79 ± 0.53 nM), 0.00067 ± 0.00025 μg/ml (0.83 ± 0.31 nM), and 0.00047 ± 0.00008 μg/ml (0.58 ± 0.099 nM), respectively. Conclusion: Docetaxel pharmacokinetics are similar for the weekly and 3-weekly regimens. Prolonged circulation of low nanomolar concentrations of docetaxel may contribute to the mechanism of action of docetaxel through suppression of microtubule dynamics and tumor angiogenesis and enhanced cell radiosensitivity in combined modality therapy.

Original languageEnglish (US)
Pages (from-to)1976-1983
Number of pages8
JournalClinical Cancer Research
Volume10
Issue number6
DOIs
StatePublished - Mar 15 2004

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docetaxel
Pharmacokinetics
Appointments and Schedules
irinotecan
Combined Modality Therapy
Radiation Tolerance

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Comparative Pharmacokinetics of Weekly and Every-Three-Weeks Docetaxel. / Baker, Sharyn D.; Zhao, Ming; Lee, Carlton K; Verweij, Jaap; Zabelina, Yelena; Brahmer, Julie; Wolff, Antonio C; Sparreboom, Alex; Carducci, Michael A.

In: Clinical Cancer Research, Vol. 10, No. 6, 15.03.2004, p. 1976-1983.

Research output: Contribution to journalArticle

Baker, Sharyn D. ; Zhao, Ming ; Lee, Carlton K ; Verweij, Jaap ; Zabelina, Yelena ; Brahmer, Julie ; Wolff, Antonio C ; Sparreboom, Alex ; Carducci, Michael A. / Comparative Pharmacokinetics of Weekly and Every-Three-Weeks Docetaxel. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 6. pp. 1976-1983.
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abstract = "Purpose: Weekly administration of docetaxel has demonstrated comparable efficacy together with a distinct toxicity profile with reduced myelosuppression, although pharmacokinetic data with weekly regimens are lacking. The comparative pharmacokinetics of docetaxel during weekly and once every 3 weeks (3-weekly) administration schedules were evaluated. Experimental Design: Forty-six patients received weekly docetaxel (35 mg/m2) as a 30-min infusion alone (n = 8) or in combination with irinotecan (n = 12), or in 3-weekly regimens, as a 1-h infusion at 60 mg/m2 with doxorubicin (n = 10), 75 mg/m2 alone (n = 9), or 100 mg/m2 alone (n = 7). Serial blood samples were obtained immediately before and up to 21 days after the infusion. Plasma concentrations were measured by liquid chromatography-mass spectrometry and analyzed by compartmental modeling. Results: Mean ± SD docetaxel clearance values were similar with weekly and 3-weekly schedules (25. 2 ± 7.7 versus 23.7 ± 7.9 liter/h/m2); half-lives were also similar with both schedules of administration (16.5 ± 11.2 versus 17.6 ± 7.4 h). With extended plasma sampling beyond 24 h post-infusion, docetaxel clearance was 18{\%} lower and the terminal half-life was 5-fold longer. At 35 mg/m2, the mean ± SD docetaxel concentration on day 8 was 0.00088 ± 0.00041 μg/ml (1.08 ± 0.51 nM) at 75 mg/m 2, concentrations on day 8, 15, and 22 were 0.0014 ± 0.00043 μg/ml (1.79 ± 0.53 nM), 0.00067 ± 0.00025 μg/ml (0.83 ± 0.31 nM), and 0.00047 ± 0.00008 μg/ml (0.58 ± 0.099 nM), respectively. Conclusion: Docetaxel pharmacokinetics are similar for the weekly and 3-weekly regimens. Prolonged circulation of low nanomolar concentrations of docetaxel may contribute to the mechanism of action of docetaxel through suppression of microtubule dynamics and tumor angiogenesis and enhanced cell radiosensitivity in combined modality therapy.",
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T1 - Comparative Pharmacokinetics of Weekly and Every-Three-Weeks Docetaxel

AU - Baker, Sharyn D.

AU - Zhao, Ming

AU - Lee, Carlton K

AU - Verweij, Jaap

AU - Zabelina, Yelena

AU - Brahmer, Julie

AU - Wolff, Antonio C

AU - Sparreboom, Alex

AU - Carducci, Michael A

PY - 2004/3/15

Y1 - 2004/3/15

N2 - Purpose: Weekly administration of docetaxel has demonstrated comparable efficacy together with a distinct toxicity profile with reduced myelosuppression, although pharmacokinetic data with weekly regimens are lacking. The comparative pharmacokinetics of docetaxel during weekly and once every 3 weeks (3-weekly) administration schedules were evaluated. Experimental Design: Forty-six patients received weekly docetaxel (35 mg/m2) as a 30-min infusion alone (n = 8) or in combination with irinotecan (n = 12), or in 3-weekly regimens, as a 1-h infusion at 60 mg/m2 with doxorubicin (n = 10), 75 mg/m2 alone (n = 9), or 100 mg/m2 alone (n = 7). Serial blood samples were obtained immediately before and up to 21 days after the infusion. Plasma concentrations were measured by liquid chromatography-mass spectrometry and analyzed by compartmental modeling. Results: Mean ± SD docetaxel clearance values were similar with weekly and 3-weekly schedules (25. 2 ± 7.7 versus 23.7 ± 7.9 liter/h/m2); half-lives were also similar with both schedules of administration (16.5 ± 11.2 versus 17.6 ± 7.4 h). With extended plasma sampling beyond 24 h post-infusion, docetaxel clearance was 18% lower and the terminal half-life was 5-fold longer. At 35 mg/m2, the mean ± SD docetaxel concentration on day 8 was 0.00088 ± 0.00041 μg/ml (1.08 ± 0.51 nM) at 75 mg/m 2, concentrations on day 8, 15, and 22 were 0.0014 ± 0.00043 μg/ml (1.79 ± 0.53 nM), 0.00067 ± 0.00025 μg/ml (0.83 ± 0.31 nM), and 0.00047 ± 0.00008 μg/ml (0.58 ± 0.099 nM), respectively. Conclusion: Docetaxel pharmacokinetics are similar for the weekly and 3-weekly regimens. Prolonged circulation of low nanomolar concentrations of docetaxel may contribute to the mechanism of action of docetaxel through suppression of microtubule dynamics and tumor angiogenesis and enhanced cell radiosensitivity in combined modality therapy.

AB - Purpose: Weekly administration of docetaxel has demonstrated comparable efficacy together with a distinct toxicity profile with reduced myelosuppression, although pharmacokinetic data with weekly regimens are lacking. The comparative pharmacokinetics of docetaxel during weekly and once every 3 weeks (3-weekly) administration schedules were evaluated. Experimental Design: Forty-six patients received weekly docetaxel (35 mg/m2) as a 30-min infusion alone (n = 8) or in combination with irinotecan (n = 12), or in 3-weekly regimens, as a 1-h infusion at 60 mg/m2 with doxorubicin (n = 10), 75 mg/m2 alone (n = 9), or 100 mg/m2 alone (n = 7). Serial blood samples were obtained immediately before and up to 21 days after the infusion. Plasma concentrations were measured by liquid chromatography-mass spectrometry and analyzed by compartmental modeling. Results: Mean ± SD docetaxel clearance values were similar with weekly and 3-weekly schedules (25. 2 ± 7.7 versus 23.7 ± 7.9 liter/h/m2); half-lives were also similar with both schedules of administration (16.5 ± 11.2 versus 17.6 ± 7.4 h). With extended plasma sampling beyond 24 h post-infusion, docetaxel clearance was 18% lower and the terminal half-life was 5-fold longer. At 35 mg/m2, the mean ± SD docetaxel concentration on day 8 was 0.00088 ± 0.00041 μg/ml (1.08 ± 0.51 nM) at 75 mg/m 2, concentrations on day 8, 15, and 22 were 0.0014 ± 0.00043 μg/ml (1.79 ± 0.53 nM), 0.00067 ± 0.00025 μg/ml (0.83 ± 0.31 nM), and 0.00047 ± 0.00008 μg/ml (0.58 ± 0.099 nM), respectively. Conclusion: Docetaxel pharmacokinetics are similar for the weekly and 3-weekly regimens. Prolonged circulation of low nanomolar concentrations of docetaxel may contribute to the mechanism of action of docetaxel through suppression of microtubule dynamics and tumor angiogenesis and enhanced cell radiosensitivity in combined modality therapy.

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