Table 1.

Results for SNS-314 CI50 drug combination screen conducted in HCT116c or HCT116p53 cells under three dosing schedules

ScheduleCell lineCombinationRatio (314/panel)
High/highHigh/lowLow/high
Mean(±) 95% CIPResultMean(±) 95% CIPResultMean(±) 95% CIPResult
(A) Concurrent administrationHCT116cSNS-3141.000.42Control1.000.23Control1.000.29Control
Carbo1.360.490.562Additive1.250.260.003Antagonistic1.780.850.003Antagonistic
GEM1.410.430.003Antagonistic1.450.690.023Antagonistic0.830.490.436Additive
5-FU1.250.100.009Antagonistic1.470.28<0.0001Antagonistic0.960.130.853Additive
SN381.350.320.076Additive1 431.440.106Additive1.060.610.635Additive
Dauno1.620.410.008Antagonistic1.701.060.004Antagonistic1.040.410.635Additive
DTX1.210.480.143Additive1.320.420.005Antagonistic1.160.310.105Additive
VIN1.050.210.492Additive2.130.530.000Antagonistic1.080.240.492Additive
HCT116p53SNS-3141.000.37Control1.000.35Control1.000.56Control
Carbo1.310.490.056Additive1.240.760.016Antagonistic1.700.610.003Antagonistic
GEM1.370.340.003Antagonistic1.740.780.001Antagonistic0.890.630.481Additive
5-FU1.330.630.123Additive1.741 340.004Antagonistic0.980.620.971Additive
SN381.290.750.036Antagonistic1.630.650.014Antagonistic1.340.940.142Additive
Dauno1.300.930.054Additive1.761 420.004Antagonistic1.541.700.076Additive
DTX1.340.440.043Antagonistic1.430.580.006Antagonistic1.020.450.720Additive
VIN0.760.340.023Synergistic2.561.610.000Antagonistic0.560.260.005Synergistic
(B) Sequential SNS-314 Embedded Image panelHCT116p53SNS-3141.000.20Control1.000.35Control1.000.54Control
Carbo0.910.540.428Additive0.840.650.118Additive0.880.280.562Additive
GEM1.181.340.965Additive0.810.600.274Additive0.860.480.274Additive
5-FU0.970.510.573Additive0.960.510.633Additive0.760.330.083Additive
DTX0.920.470.237Additive0.850.520.237Additive1.000.260.697Additive
VIN1.311.010.054Additive0.750.600.142Additive0.600.270.024Synergistic
HCT116p53SNS-3141.000.31Control1.000.37Control1.000.40Control
Carbo0.810.650.220Additive0.810.230.118Additive1.531.570.056Additive
GEM0.950.440.965Additive0.950.590.633Additive1.561.260.068Additive
5-FU1.360.820.173Additive1.001.020.408Additive2.951.68<0.0001Antagonistic
DTX0.860.350.083Additive0.830.330.122Additive1.200.640.122Additive
VIN1.742.780.240Additive0.941.070.733Additive1.492.240.188Additive
(C) Sequential panel Embedded Image SNS-314HCT116cSNS-3141.000.30Control1.000.48Control1.000.26Control
Carbo1.200.760.108Additive0.931.120.345Additive2.103.260.029Antagonistic
GEM1.200.730.279Additive0.870.290.235Additive0.960.770.574Additive
5-FU0.950.410.798Additive0.910.260.442Additive1.130.970.721Additive
DTX1.120.470.505Additive0.860.470.130Additive1.110.320.279Additive
VIN1.022.050.933Additive1.330.880.214Additive1.081.191.000Additive
HCT116p53SNS-3141.000.33Control1.000.26Control1.000.42Control
Carbo1.331.250.228Additive1.272.850 755Additive2.443.260.020Antagonistic
GEM1.210.720.328Additive0.710.410.021Synergistic0.980.550.959Additive
5-FU1.060.390.798Additive0.840.450.195Additive1.651.380.065Additive
DTX1.130.210.195Additive0.950.440.505Additive1.400.700.065Additive
VIN1.070.670.570Additive1 210.560.073Additive1.060.310.808Additive

NOTE: Deviation for an additive response (where the CI50 = 1) was scored when the 95% confidence interval was statically distinct from the SNS-314 additive internal control (P < 0.05). A CI50 < 1 was scored as synergistic; CI50 > 1 was scored as antagonistic.

Abbreviations: Carbo, carboplatin; GEM, gemcitabine; Dauno, daunomycin; DTX, docetaxel; VIN, vincristine; 95% CI, 95% confidence interval.