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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.

Brunsvig PF, Andersen A, Aamdal S, Kristensen V, Olsen H - BMC Cancer (2007)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Oncology, Cancer Clinic, Rikshospitalet-Radiumhospitalet Medical Centre, Montebello, 0310 Oslo, Norway. p.f.brunsvig@medisin.uio.no

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.

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Elimination curve for patients receiving 20 mg/m2 of docetaxel. Mean values (▼), with error bars representing 1SD. Gray lines represent the extreme values at each time point. Vertical arrows labelled Rad represent the time of radiation treatment.
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Figure 1: Elimination curve for patients receiving 20 mg/m2 of docetaxel. Mean values (▼), with error bars representing 1SD. Gray lines represent the extreme values at each time point. Vertical arrows labelled Rad represent the time of radiation treatment.

Mentions: The time schedule between radiotherapy and plasma concentration of docetaxel is illustrated in Figure 1. Docetaxel was detectable in all samples taken at 72 hours (n = 14). Median concentration 3.0 nM (0.7–6.5).


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.

Brunsvig PF, Andersen A, Aamdal S, Kristensen V, Olsen H - BMC Cancer (2007)

Elimination curve for patients receiving 20 mg/m2 of docetaxel. Mean values (▼), with error bars representing 1SD. Gray lines represent the extreme values at each time point. Vertical arrows labelled Rad represent the time of radiation treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2175508&req=5

Figure 1: Elimination curve for patients receiving 20 mg/m2 of docetaxel. Mean values (▼), with error bars representing 1SD. Gray lines represent the extreme values at each time point. Vertical arrows labelled Rad represent the time of radiation treatment.
Mentions: The time schedule between radiotherapy and plasma concentration of docetaxel is illustrated in Figure 1. Docetaxel was detectable in all samples taken at 72 hours (n = 14). Median concentration 3.0 nM (0.7–6.5).

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Oncology, Cancer Clinic, Rikshospitalet-Radiumhospitalet Medical Centre, Montebello, 0310 Oslo, Norway. p.f.brunsvig@medisin.uio.no

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.

Show MeSH
Related in: MedlinePlus