Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin in advanced non-small cell lung cancer (NSCLC) patient.

8051 Background: Variability of chemotherapy exposure may cause severe toxicity or lack of efficacy. Paclitaxel (PTX) exposure (time above a plasma concentration of 0.05mM, Tc > 0.05) has been shown to predict toxicity. Whereas carboplatin dose is adapted to kidney function, PTX dosing only accounts for body-surface area. We developed a PTX dosing algorithm for avoidance of supra- or subtherapeutic PTX exposure based on Tc > 0.05 determined from a single blood sample drawn 18-30 hours after starting PTX infusion. This study was initiated to validate PK-guided PTX dosing in advanced NSCLC patients. Methods: 304 patients with advanced NSCLC were randomly assigned to receive up to 6 cycles of first-line 3-weekly carboplatin AUC 6 combined with PTX either at a standard dose of 200mg/m2 (Arm A) or at a PK-guided dose (Arm B). Initial PTX dose in Arm B was between 150 to 200 mg/m2 based on age and sex, and subsequent PTX doses were adjusted according to the previous cycle PTX Tc > 0.05 to target a Tc > 0.05 bet...