Table 3.
In vitro combination study of IGF-IR inhibitor BMS-536924 with Her1/Her2 inhibitors gefitinib or BMS-690514 in Rh36 cell lines
| Ratio of BMS-536924/gefitinib or BMS-690514 in combination | Combining with gefitinib | Combining with BMS-690514 | ||
|---|---|---|---|---|
| Combination index with SE | 95% CI for Combination index | Combination index with SE | 95% CI for Combination index | |
| 9:1 | 1.09 ± 0.20 | 0.69–1.49 | 0.69 ± 0.09 | 0.52–0.87 |
| 4:1 | 1.01 ± 0.19 | 0.63–1.39 | 0.63 ± 0.08 | 0.46–0.79 |
| 2:1 | 1.01 ± 0.20 | 0.63–1.40 | 0.47 ± 0.05 | 0.37–0.57 |
| 1:1 | 0.89 ± 0.15 | 0.60–1.18 | 0.46 ± 0.06 | 0.34–0.58 |
| 1:2 | 0.98 ± 0.14 | 0.70–1.26 | 0.47 ± 0.07 | 0.33–0.61 |
| 1:4 | 0.89 ± 0.11 | 0.67–1.10 | 0.48 ± 0.08 | 0.32–0.64 |
NOTE: A dilution of ratios of drug combination method was used in cellular proliferation assays to test the IC50 values of single agents, as well as in combination. Combination indices, SEs, and 95% confidence intervals were calculated for the different ratios and used to determine if the combination results represent synergistic, additive, or antagonistic effects when two compounds were added simultaneously. The combination results were analyzed by Isobolograms. Combination index ± 2× SE <1 indicates synergy and >1 indicates additivity. Synergistic efforts observed for IGF-IR inhibitor BMS-536924 in combination with BMS-690514, a Her1/Her2 inhibitor. Additive effort of BMS-536924 in combination with gefitinib was observed.