Table 3.
Pharmacokinetic Parameters of Erlotinib and OSI-420 Metabolite.
| Parameter | Erlotinib alone (E)(Day 14 ± 4) | Erlotinib + Dovitinib (E + D)(Day 29 ± 4) | Geometric mean ratio (D + E:E)
|
|
|---|---|---|---|---|
| Mean | 95% CI | |||
| Erlotinib–150 mg dose (n = 6)a | ||||
| Cmax (ng/ml) | 2308 ± 698 | 317 ± 303* | 0.07 | 0.01–0.59 |
| Tmax (h) | 3 (2–24) | 3 (2–6) | – | – |
| T1/2, terminal(h) | 50 ± 53 | 5 ± 3* | 0.10 | 0.02–0.42 |
| AUC0–24h (ng/ml × h) | 41030 ± 15577 | 1858 ± 1790* | 0.03 | 0.004–0.18 |
| OSI-420 (n = 5) b | ||||
| Cmax (ng/ml) | 317 ± 166 | 56 ± 43* | 0.17 | 0.07–0.40 |
| AUC0–24h (ng/ml × h) | 5381 ± 2982 | 342 ± 252* | 0.06 | 0.02–0.17 |
All values reported as mean ± standard deviation except Tmax represented as median and range. All values with a (*) indicate a statistically significant change with the combination of erlotinib + dovitinib versus erlotinib alone at a 2-sided p-value < 0.05.
a
One patient had a dose reduction in erlotinib from 150 mg to 100 mg and this patient’s PK parameters were normalized to a 150 mg dose.
b
One patient was excluded from OSI-420 analysis since all concentrations were below the lower limits of quantification at day 29 ± 4.