Table 1. Best-fit models for single treatment with erlotinib and G→E sequence.
| A | ||||||||
|---|---|---|---|---|---|---|---|---|
| During treatment | After treatment | |||||||
| BxPC-3 | Delay S(> 6 h) | G2M blocking probability(> 6 h) | G1 blocking probability | Delay S | S deathrate(cells/h) | Delay S | Delay G2M | G1 recycling |
| generation 0 | generation 0 | generation 1 | generation 1 | generation 0/1 | generation 1 | generation 1 | generation 0/1 | |
| 1 μMerlotinib | 0.33 [0.30–0.35] |
0.11 [0.08–0.14] |
0.23 [0.21–0.25] |
0.33 [0.30–0.35] |
0.010 [0.008–0.011] |
0.41 [0.36–0.45] |
0.19 [0.04–0.30] |
0.03 [0.02–0.04] |
| 20G→1E | ND | 0.11 [0–0.27] |
0.23 [0.13–0.32] |
0.15 [0–0.28] |
0 [0–0.012] |
0.58 [0.51–0.65] |
0.59 [0.24–0.71] |
0.07 [0.03–0.12] |
| 40G→1E | ND | 0.16 [0–0.31] |
0 [0–0.10] |
0.27 [0.17–0.40] |
0.016 [0.004–0.028] |
0.60 [0.53–0.66] |
0.58 [0.35–0.68] |
ND |
| 10 μMerlotinib | 0.93 [0.91–0.96] |
0.23 [0.19–0.27] |
0.98 [0.97–0.996] |
0 [0–0.09] |
0.014 [0.012–0.016] |
0.41 [0.39–0.44] |
0.28 [0.18–0.36] |
0.24 [0.21–0.26] |
| 20G→10E | ND | 0.07 [0–0.23] |
0.83 [0.70–0.91] |
0 [0–0.19] |
0.002 [0–0.020] |
0.56 [0.51–0.61] |
0.75 [0.63–0.82] |
0.17 [0.13–0.21] |
| 40G→10E | ND | 0.10 [0–0.23] |
0.91 [0.74–1.0] |
0 [0–0.28] |
0.018 [0.002–0.034] |
0.55 [0.50–0.60] |
0.59 [0.42–0.69] |
0.23 [0.20–0.24] |
| B | ||||||||
|---|---|---|---|---|---|---|---|---|
| During treatment | After treatment | |||||||
| Capan-1 | Delay S | G2M blocking probability(> 6 h) | G1 blocking probability | Delay S | S deathrate(cells/h) | Delay S | G1 recycling | |
| generation 0 | generation 0 | generation 1 | generation 1 | generation 0 | generation 1 | generation 0/1 | ||
| 1 μMerlotinib | ND | 0 [0–0.39] |
0.33 [0.18–0.47] |
0 [0–0.43] |
0 [0–0.018] |
ND | 0.03 [0.01–0.06] |
|
| 30G→1E | ND | 0 [0–0.18] |
0.33 [0.21–0.49] |
ND | 0 [0–0.037] |
ND | 0.03 [0.01–0.07] |
|
| 100G→1E |
0.78 (> 0 h) [0.70–0.82] |
0 [0–0.17] |
0 [0–0.13] |
ND | 0 [0–0.008] |
ND | ND | |
| 10 μMerlotinib | 0.85 (> 6 h) [0.78–0.91] |
0.06 [0–0.15] |
0.47 [0.38–0.57] |
0 [0–0.39] |
0 [0–0.004] |
0.48 [0.37–0.58] |
0.06 [0.03–0.10] |
|
| 30G→10E | ND | 0.06 [0–0.22] |
0.47 [0.37–0.65] |
0.48 [0.19–0.54] |
0 [0–0.017] |
0.48 [0.19–0.54] |
0.06 [0.01–0.10] |
|
| 100G→10E |
0.81 (> 0 h) [0.69–0.90] |
0.06 [0–0.19] |
0.29 [0.10–0.47] |
0.45 [0.30–0.56] |
0 [0–0.004] |
0.45 [0.30–0.56] |
0.06 [0.01–0.19] |
|
Shown in bold characters are the parameters describing the effects of the last administered drug that have to be changed to reproduce the experimental data of the combinations. The likelihood-based 95% confidence intervals for each parameter are in square bracket.
ND: not detectable, i.e. data were not sensitive for evaluation of the parameter. Short term G1 block was always ND with the combination (not shown). Parameters of erlotinib or the combination G→E were compared for BxPC-3 (panel A) and Capan-1 (panel B).