Abstract 2592: Anti-tumor activity of icotinib (BPI-2009H) and BPI-403B in the BxPC-3 pancreatic cancer cell line

Abstract

Abstract Introduction: The purpose of this research was to investigate the anti-tumor effect of BPI-2009H and BPI-403B, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in the human pancreatic cancer cell lines BxPC-3 and Panc-1, in vitro and in vivo and determine the maximum tolerated dose (MTD) of the compound in mouse. Experimental Design: In vitro, human pancreatic cancer cell lines, BxPC-3 and Panc-1 were exposed to varying concentrations of BPI-2009H and BPI-403B, the concentration of compound required to inhibit growth by fifty percent (IC50) was estimated. In vivo, tumor growth inhibition of low dose BPI-2009H was tested in xenografted nude mice with BxPC-3 pancreatic cancer tumors. The maximum tolerated dose (MTD) was established via oral administration of low, mid and high doses to Harlan mice of both BPI-2009H and BPI-403B. Upon determination of the MTD, the in vivo efficacy of high dose BPI-2009H was evaluated via tumor growth inhibition study on xenografted nude mice with BxPC-3 pancreatic cancer tumors. Results: BPI-2009H, as a single agent, inhibited the growth of BxPC-3 cells in a dose dependent manner, with a relative IC50 value of 25.8 μM. BPI-403B, as a single agent, inhibited growth of BxPC-3 cells in a dose dependent manner as well, with a relative IC50 value of 2.7 μM. BPI-2009H and BPI-403B were tested up to 50μM in Panc-1 cells with no apparent effect at the upper limit of the study for either of the compounds. In vivo, the mice treated with BPI-403B demonstrated a statistically significant tumor growth delay, 14.3 days. 20% of the mice experienced tumor regression. The compound was well tolerated with minimal body weight loss. At low doses, BPI-2009H did not show any statistically significant tumor growth delay, but upon increasing the dose to the MTD, significant signs of anticancer activity was demonstrated, with an increase in tumor growth delay. Conclusions: The in vitro and in vivo findings show that both BPI-2009H and BPI-403B have antiproliferative effects against BxPC-3 pancreatic cancer cells. These compounds are both well tolerated and may prove to be an alternative option of EGFR-TKI to erlotinib treatment in pancreatic cancer cases. Citation Format: Victoria Lynn Wilde, Don Zhang, Jirong Peng, Michael A. Green, Michael N. Greco, Michael Costanzo. Anti-tumor activity of icotinib (BPI-2009H) and BPI-403B in the BxPC-3 pancreatic cancer cell line. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2592. doi:10.1158/1538-7445.AM2015-2592