Clinical pharmacokinetics, safety, and preliminary efficacy evaluation of icotinib in patients with advanced non-small cell lung cancer

Objectives: To receive pharmacokinetics, safety, and anti-tumor activity of icotinib, a novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), in patients-with advanced non-small-cell lung cancer (NSCLC). Materials and methods: Patients (n=40) with advanced NSCLC were enrolled to receive escalating doses of icotinib, which was administrated on Day 1 followed by 28-day continuous dosing starting from Day 4. Four dosing regimens, 100 mg b.i.d., 150 mg b.i.d., 125 mg t.i.d., and 200 mg b.i.d. were studied. Pharmacokinetics (PK), safety, and efficacy of icotinib were evaluated. Results: Icotinib was well tolerated in Chinese patients with refractory NSCLC. No toxicity with >3 grades were reported in more than 2 patients under any dose levels. One complete response (3%) and 9 partial responses (23%) were received. Total disease control rate could reach at 73% and median progress-free survival (range) was 154(17-462) days. PK exposure of icotinib increased with increase of dose in NSCLC patients. Food was suggested to increase PK exposure by similar to 30%. Mean t(1/2 beta) was within 5.31-8.07 h. No major metabolite (>10% plasma exposure of icotinib) was found in NSCLC patients. Conclusions: Icotinib with up to 400 mg/day exhibited good tolerance and preliminary antitumor activity in Chinese NSCLC patients. Pharmacokinetics of icotinib and 5 major metabolites were fully investigated in NSCLC patients. Optimized biologic dose (OBD) was finally recommended to be 125 mg t.i.d. for the later clinical study. (C) 2015 Elsevier Ireland Ltd. All rights reserved.