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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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The relationship between AAG-level and docetaxel AUC for patients receiving 100 mg/m2 of docetaxel (RSQ = 0.64, p < 0.0001).
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Figure 2: The relationship between AAG-level and docetaxel AUC for patients receiving 100 mg/m2 of docetaxel (RSQ = 0.64, p < 0.0001).

Mentions: The correlation between AUC and AAG was significant for the 100 mg/m2 group of patients (Figure 2) but not for the 20 mg/m2 group of patients (RSQ = 0.02, p = 0.863). For the individual patient in the 20 mg/m2 group however, the difference in docetaxel AUC between the first and second course correlated with the change in AAG levels between the first and second course (Figure 3).


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)

The relationship between AAG-level and docetaxel AUC for patients receiving 100 mg/m2 of docetaxel (RSQ = 0.64, p < 0.0001).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: The relationship between AAG-level and docetaxel AUC for patients receiving 100 mg/m2 of docetaxel (RSQ = 0.64, p < 0.0001).
Mentions: The correlation between AUC and AAG was significant for the 100 mg/m2 group of patients (Figure 2) but not for the 20 mg/m2 group of patients (RSQ = 0.02, p = 0.863). For the individual patient in the 20 mg/m2 group however, the difference in docetaxel AUC between the first and second course correlated with the change in AAG levels between the first and second course (Figure 3).

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