Randomized study of individualized pharmacokinetically-guided dosing of paclitaxel compared with body-surface area dosing in Chinese patients with advanced non-small cell lung cancer

Abstract

Aims: This prospective, randomized study was initiated to assess the impact of pharmacokinetically (PK)-guided paclitaxel (PTX) dosing on toxicity and efficacy compared with body-surface area (BSA)-based dosing in Chinese non-small cell lung cancer patients. Methods: A total of 319 stage IIIB/IV non-small cell lung cancer patients receiving first-line chemotherapy were enrolled. Patients were randomized to receive 3-weekly carboplatin plus PTX at a starting dose of 175 mg/m2 with subsequent PTX dosing based on either BSA or PK-guided dosing targeting time above a PTX plasma concentration of 0.05 μmol/L (PTXTc > 0.05) between 26 and 31 hours. The primary safety endpoint was grade 4 haematological toxicity. The secondary endpoints were neuropathy, objective response rate, progression-free survival and overall survival. Results: In total, 275 (86%) patients completed ≥2 cycles of chemotherapy (140 in BSA arm and 135 in PK arm). In cycle 1, with the same PTX dose, average PTXTc > 0.05 was 37 hours (range = 18–57 hours). Over cycles 2–4, patients in the PK arm had significantly lower average PTX doses and exposure compared with the BSA arm (128 vs 161 mg/m2, P