ORIGINAL REPORTS Phase I and Pharmacokinetics Gemcitabine and Paclitaxel: Pharmacokinetic and Pharmacodynamic Interactions in Patients With Non Small Cell Lung Cancer

Purpose: To assess possible pharmacokinetic and pharmacodynamic interactions between gemcitabine and paclitaxel in a phase I/II study in non-small-cell lung cancer (NSCLC) patients. Patients and Methods: Eighteen patients with advanced NSCLC received the following in a 3-week schedule: gemcitabine 1,000 mg/m2 (30 minutes, days 1 and 8) and paclitaxel 150 (n = 9) or 200 mg/m2 (n = 9) before gemcitabine (3 hours, day 1). Plasma pharmacokinetics and pharmacodynamics in mononuclear cells were studied. Results: Gemcitabine did not influence paclitaxel pharmacokinetics at 150 and 200 mg/m2 (area under the concentration-time curve (AUC), 7.7 and 8.8 mumol/L cntdot h, respectively; maximum plasma concentration (Cmax), 3.2 and 4.0 mumol/L, respectively), and paclitaxel did not influence that of gemcitabine (Cmax, 30 +- 3 mumol/L) and 2',2'-difluorodeoxyuridine. Paclitaxel, however, dose …