Limits...
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.

Show MeSH

Related in: MedlinePlus

Interpatient variations for two docetaxel dose levels. Plotting the total range (dotted line = median) of docetaxel concentrations at each time point, the graphs for the patients receiving 20 mg/m2 and the patients receiving 100 mg/m2 will overlap at some time points (e.g. at 6 h: low dose range 18–55 nM, high dose range 51–304 nM). For simplicity, the graph shows determinations from 2 to 25 hours.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2175508&req=5

Figure 4: Interpatient variations for two docetaxel dose levels. Plotting the total range (dotted line = median) of docetaxel concentrations at each time point, the graphs for the patients receiving 20 mg/m2 and the patients receiving 100 mg/m2 will overlap at some time points (e.g. at 6 h: low dose range 18–55 nM, high dose range 51–304 nM). For simplicity, the graph shows determinations from 2 to 25 hours.

Mentions: It is established that the pharmacokinetic profile of docetaxel is characterized by substantial inter-patient variability. Bruno et al [7] reported a 3.5 fold variation in clearance in 600 patients receiving 75–100 mg/m2 of docetaxel. Similarly, our results showed AUC values differing 3.5 fold for the 100 mg/m2 group and more than 2 fold for the 20 mg/m2 group. Plasma concentrations for the two groups were even overlapping at some time points (Figure 4). Most previous pharmacokinetic data for docetaxel originates from studies with 75–100 mg/m2 infused over 1 hour every third week. Pharmacokinetic data for docetaxel at such high doses follow a three compartment model with half-lives of 4 minutes, 38 minutes and 12 hours in the α, β and γ phase respectively up to 24 hours post infusion. Total body clearance is 21 L/h/m2, and the volume of distribution at steady state (Vss) is 74 L/m2 [9]. In a study by Baker et al [19] comparing pharmacokinetics of weekly- and 3-weekly docetaxel, it was demonstrated that the docetaxel pharmacokinetics are similar for the two dose levels. Our results are in accordance with their findings, in our study the clearance was 22 (10–34) L/h/m2 for the high dose patients and 19 (14–29) L/h/m2 for the low dose patients.


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)

Interpatient variations for two docetaxel dose levels. Plotting the total range (dotted line = median) of docetaxel concentrations at each time point, the graphs for the patients receiving 20 mg/m2 and the patients receiving 100 mg/m2 will overlap at some time points (e.g. at 6 h: low dose range 18–55 nM, high dose range 51–304 nM). For simplicity, the graph shows determinations from 2 to 25 hours.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Interpatient variations for two docetaxel dose levels. Plotting the total range (dotted line = median) of docetaxel concentrations at each time point, the graphs for the patients receiving 20 mg/m2 and the patients receiving 100 mg/m2 will overlap at some time points (e.g. at 6 h: low dose range 18–55 nM, high dose range 51–304 nM). For simplicity, the graph shows determinations from 2 to 25 hours.
Mentions: It is established that the pharmacokinetic profile of docetaxel is characterized by substantial inter-patient variability. Bruno et al [7] reported a 3.5 fold variation in clearance in 600 patients receiving 75–100 mg/m2 of docetaxel. Similarly, our results showed AUC values differing 3.5 fold for the 100 mg/m2 group and more than 2 fold for the 20 mg/m2 group. Plasma concentrations for the two groups were even overlapping at some time points (Figure 4). Most previous pharmacokinetic data for docetaxel originates from studies with 75–100 mg/m2 infused over 1 hour every third week. Pharmacokinetic data for docetaxel at such high doses follow a three compartment model with half-lives of 4 minutes, 38 minutes and 12 hours in the α, β and γ phase respectively up to 24 hours post infusion. Total body clearance is 21 L/h/m2, and the volume of distribution at steady state (Vss) is 74 L/m2 [9]. In a study by Baker et al [19] comparing pharmacokinetics of weekly- and 3-weekly docetaxel, it was demonstrated that the docetaxel pharmacokinetics are similar for the two dose levels. Our results are in accordance with their findings, in our study the clearance was 22 (10–34) L/h/m2 for the high dose patients and 19 (14–29) L/h/m2 for the low dose patients.

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