Effects of dexamethasone (Dex) pretreatment on toxicity and efficacy of carboplatin and gemcitabine (Carbo/Gem) in patients with non-small cell lung cancer (NSCLC)

18124 Background: Our preclinical data showed that treating mice with Dex 4 days prior to chemotherapy increased efficacy and decreased toxicity of Carbo/Gem in nude mice bearing human NSCLC by increasing drug concentration in tumors, and decreasing drug concentration in normal tissue without altering plasma pharmacokinetics (PK). Thus, we undertook a Phase I/II trial to determine the optimal dose of Dex, and the effect of Dex on Carbo/Gem plasma PK. Methods: Patients (n=30) with untreated, stage IV NSCLC and PS =2 received Gem, 1g/m2 days 1&8, and Carbo, AUC 5.5 on day 1. Patients were randomized (1:2:2) to receive no Dex (arm 1), or Dex at 8 and 16 mg bid po 4 days before and on day 1 (arms 2 and 3). Dex was administered in courses 2, 3, and 4 (only) to allow course 1 vs course 2 intra-patient toxicity and Carbo/Gem plasma PK assessment. Plasma samples were analyzed by HPLC for Carbo/Gem. Plasma PK analysis was performed with NONMEM v5 using a 5-compatment or 2-compartment structural models for Gem and ...