Table 3.
Erlotinib and 5-Fluorouracil Pharmacokinetic Parametersa
| Pharmacokinetic Parameter | DL 1 | DL 2b | DL 3 | |||
|---|---|---|---|---|---|---|
| Single Agent | Combination | Single Agent | Combination | Single Agent | Combination | |
| Erlotinib | ||||||
| Cmax (ng/mL) | 610.8 ± 100.8 (3) | 1152.2 ± 426.3 (3) | 985.4 ± 575.5 (8) | 1993.0 ± 980.5 (7) | 1958.4 ± 1158.5 (3) | 4446.5 ± 1066.6 (3) |
| Tmax (hour) | 1.08 (1.00–2.00, 3) | 4.00 (2.00–4.08, 3) | 2.00 (1.03–4.02, 8) | 2.00 (1.00–10.00, 7) | 6.00 (1.00–24.08, 3) | 4.02 (1.03–4.17, 3) |
| AUC (ng/hour/mL) | 14172, 16276 (2) | 10848, 61493 (2) | 40231 ± 49115 (7) | 52684 ± 35964 (7) | 39894, 62060 (2) | 154957 ± 75031 (3) |
| OSI-420 | ||||||
| Cmax (ng/mL) | 60.8 ± 16.1 (3) | 86.1 ± 26.4 (3) | 67.8 ± 49.1 (8) | 158.3 ± 105.9 (7) | 193.2 ± 92.6 (3) | 748.0 ± 269.5 (3) |
| Tmax (hour) | 2.00 (1.08–2.00, 3) | 4.00 (2.00–6.00, 3) | 3.00 (1.03–25.03, 8) | 2.00 (1.00–10.00, 7) | 9.95 (2.07–24.08, 3) | 6.00 (4.17–8.12, 3) |
| OSI-420:Erlotinib Cmin ratio | 0.085 ± 0.002 (3) | 0.081 ± 0.005 (3) | 0.074 ± 0.028 (8) | 0.069 ± 0.021 (8) | 0.185 ± 0.076 (3) | 0.202 ± 0.085 (3) |
| 5-Fluorouracil Cl (liter/hour) | 207.9 ± 36.0 (3) | 182.2 ± 20.9 (3) | 261.4 ± 141.4 (7) | 243.7 ± 93.6 (8) | 200.3, 217.4 (2) | 221.5, 313.2 (2) |
a
Values are reported as the arithmetic mean ± standard deviation (n). The Tmax is reported as the median (range). When n ≤ 2, individual values are reported.
b
DL2a (FOLFOX/erlotinib 100 mg) and 2b (with bevacizumab).
Abbreviations: AUC = area under the curve; DL = dose level; FOLFOX = infusional 5-fluorouracil/leucovorin/oxaliplatin