Evaluation of the Effectiveness of Two Drugs Combination Therapy In Vitro Cytotoxicity Study

• Activity Number: 527
• Type: Contributed
• Date/Time: Wednesday, August 3, 2011 : 10:30 AM to 12:20 PM
• Sponsor: Section on Statistical Consulting
• Author(s): Yufeng Li*+ and Hui-Chien Kuo and Choo Hyung Lee and Patsy Oilver and Donald Buchesbum
• Companies: University of Alabama at Birmingham and University of Alabama at Birmingham and University of Alabama at Birmingham and University of Alabama at Birmingham and University of Alabama at Birmingham
• Keywords: Synergy effect ; Drugs combination ; Nonlinear regression ; Combination index

Abstract

The cytotoxic of two drugs combination can be evaluated to assess whether the combination cytotoxic effects are additive, less than additive (antagonistic), or greater than additive (synergistic). There are several statistical methods available to evaluate these effects with different statistical properties and limitations. We evaluated the following methods using data generated from a collection of breast cancer cell lines. The methods include 1) recommended by Gennings, modeling using a second order response surface model with linear, quadratic, and interaction terms for each of the cell line. A significant interaction term was classed as either synergistic or antagonistic depending on whether the interaction term was negative with more than additive cytotoxicity or positive with less than additive cytotoxicity. 2) The combination index (CI) for dose combinations were calculated based