The combination of a Retinoid X Receptor (RXR) agonist LGD1069 (bexarotene) and vinorelbine produce synergistic growth inhibitory activity in non-small-cell lung cancer (NSCLC) cell lines

7358 Background: NSCLC is one of the leading causes of cancer-related deaths world wide. Targretin® (bexarotene) is a selective RXR agonist approved for the treatment of CTCL. Bexarotene has also shown phase I/IIa activity by enhancing survival and delaying progression in NSCLC patients (Clin Cancer Res 5:1658, 1999; J Clin Oncol 19:2626, 2001). Methods: We evaluated the anti-proliferative effects in vitro of LGD1069 as a single agent or in combination with the cytotoxic agents vinorelbine or paclitaxel in 10 NSCLC cell lines of different histologies. Cells were treated with LGD1069 alone or in combination with cytotoxic agents, growth and viability were examined. The combinations were carried out either concomitantly or sequentially. Results: LGD1069 as a single agent had modest growth inhibitory effects (at > 1 μM) in a subset of the NSCLC cell lines. LGD1069 combined with vinorelbine produced enhanced growth inhibitory activity (a left-ward shift of 3 –10 fold in the IC50) when compared to vinorelbine ...