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

BACKGROUND: Previous pharmacokinetic studies with docetaxel have mostly used 3-weekly (75 mg/m(2 )and 100 mg/m(2)) or weekly regimens (35–40 mg/m(2)). The pharmacokinetics and radiosensitizing efficacy of weekly 20 mg/m(2 )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/m(2 )regimen. METHODS: Thirty-four patients with non small cell lung cancer (NSCLC) were included in this study, 19 receiving 100 mg/m(2 )docetaxel 3-weekly as single therapy, and 15 receiving 20 mg/m(2 )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/m(2). CONCLUSION: The pharmacokinetics of docetaxel is characterized by great inter-individual variability and at some time points plasma concentrations for 20 mg/m(2 )and 100 mg/m(2 )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/m(2 )weekly docetaxel.