Bayesian pharmacokinetically guided dosing of paclitaxel in patients with non-small cell lung cancer.

PURPOSE: Paclitaxel is a taxane derivative with a profound antitumor activity against a variety of solid tumors. In a previous clinical study in patients with non-small cell lung cancer (NSCLC) treated with paclitaxel, it was shown that paclitaxel plasma concentrations of 0.1 micro mol/liter for > or = 15 h were associated with prolonged survival. The purpose of this study was to evaluate the feasibility of Bayesian dose individualization to attain paclitaxel plasma concentrations >0.1 micromol/liter for > or = 15 h. Experimental Design: Patients with stage IIIb-IV NSCLC were treated with paclitaxel and carboplatin once every 3 weeks for a maximum of six courses. During the first course, a standard paclitaxel dose of 175 mg/m(2) was administered i.v. in 3 h. In subsequent courses, the paclitaxel dose was individualized based on observed paclitaxel concentrations in plasma during the previous course(s) using a Bayesian algorithm. The paclitaxel dose of a subsequent course was increased to the lowest dose for which the predicted time period during which the paclitaxel plasma concentration exceeds 0.1 micromol/liter was >15 h. RESULTS: A total of 25 patients have been included in the study (92 evaluable courses). During the first course, the median time period above the threshold concentration was 16.3 h (range, 7.6-31.6 h), and was