A phase I/II study of bexarotene (B) and erlotinib (E): A novel targeted combination therapy for lung cancer and other aerodigestive tract (ADT) tumors

3092 Background: We reported (Proc AACR, 2701a, 2003) two important pathways in lung carcinogenesis. Treatment of BEAS-2B human bronchial epithelial cells (HBEC) with tobacco carcinogens enhanced cyclin D1 and epidermal growth factor receptor (EGFR) expression. All-trans-retinoic acid (RA) suppressed their expression through a transcriptional mechanism for EGFR and post-transcriptional proteasome-dependent proteolysis for cyclin D1. Similar effects were noted with the rexinoid (B), bypassing the need for intact RAR-β signaling often deregulated in lung cancer. We found additive cooperation in HBEC between B and EGFR tyrosine kinase inhibitor E (OSI-774) repressing G1 cyclins via non-cross-resistant pathways. Methods: Phase I/II trial of B and E in advanced ADT tumors. Primary objective - maximum tolerated dose. Secondary objectives - toxicities, efficacy, and surrogate markers of response (cyclin D1, Ki-67, EGFR, phospho-EGFR) in buccal swabs from patients (pts) at the highest dose. 3 dose levels - 1: B 3...