Bayesian Pharmacokinetically Guided Dosing of Paclitaxel in Patients with Non-Small Cell Lung Cancer

• Published in: Clinical cancer research 2004-04, Vol.10 (7), p.2237-2244
• Main Authors: DE JONGE, Milly E, VAN DEN BONGARD, H. J. G. Desirée, HUITEMA, Alwin D. R, MATHOT, Ron A. A, ROSING, Hilde, BAAS, Paul, VAN ZANDWIJK, Nico, BEIJNEN, Jos H, SCHELLENS, Jan H. M
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic agents; Antineoplastic Agents - pharmacology; Antineoplastic Agents, Phytogenic - pharmacokinetics; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Biological and medical sciences; Carboplatin - pharmacology; Carcinoma, Non-Small-Cell Lung - drug therapy; Cisplatin - pharmacology; Dose-Response Relationship, Drug; Female; Humans; Lung Neoplasms - drug therapy; Male; Medical sciences; Middle Aged; Models, Biological; Paclitaxel - pharmacokinetics; Paclitaxel - pharmacology; Pharmacology. Drug treatments; Time Factors; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-03-0060

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 μmol/liter for ≥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 μmol/liter for ≥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 μmol/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