Phase I trial of vorinostat in combination with erlotinib in advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations after erlotinib progression

e19057 Background: Vorinostat (SAHA) is a histone deacetylase inhibitor that induces differentiation, growth arrest and apoptosis of malignant cells. In vitro, there is a synergistic interaction of vorinostat in combination with gefitinib in NSCLC cell lines. Moreover, vorinostat increases levels of E-cadherin, p21, and downregulates expression of phospho-AKT and phospho-ERK1/2. These molecular findings could reverse resistance to erlotinib in mutant patients. Methods: We conducted a standard 3+3 Phase I trial of oral erlotinib 150 mg QD in combination with oral vorinostat (dose level 1 [DL1], 300 mg QD on days 1–7 every 21 days; DL2, 400 mg QD on days 1–7 every every 21 days, and; DL3, 400 mg QD on days 1–7 and 15–21 in a 28-day cycle). Cycles were repeated for a maximum of 6 cycles until progressive disease (PD) or intolerable toxicity. Pts with advanced NSCLC with EGFR mutations (Exon 19 and 21) after erlotinib progression and ECOG ≤2 were eligible. The main objectives were to determine the maximum tol...