Abstract 3601: Evaluation of a mathematical modeling framework to describe combination therapy with Gemcitabine

Abstract

Abstract The quantitative assessment of the effectiveness of chemotherapeutic combinations is of increasing interest. This is especially true given the complexities of different dosing schedules and animal model systems. This work evaluates a recently proposed mathematical modeling framework (Koch et al., J Pharmacokinet Pharmacodyn 36:179-197, 2009), and modifications thereof, for quantifying synergisms between drugs used in combination therapy based on preclinical data. In this study, we evaluated published NSCLC (H460a) tumor growth inhibition (TGI) data following treatment with Erlotinib and Gemcitabine (Higgins et al., Anticancer Drugs 15: 503-512, 2004), administered both alone and in combination. We simultaneously modeled the pharmacodynamic data from all therapeutic regimens. TGI data from both monotherapy and combination therapy were adequately described. The results suggest that Erlotinib and Gemcitabine at sub-maximal doses work in a synergistic manner to reduce tumor growth. This modeling framework may prove useful in the design and optimization of preclinical experiments involving drug combinations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3601.