Table 5.
Pharmacokinetic parameters of regorafenib alone (Day −14) or with cetuximab after a single regorafenib dose (Day 1); geometric mean (%CV)
| Day | Continuous regorafenib 60 mg plus cetuximab | Continuous regorafenib 100 mg plus cetuximab | Intermittent regorafenib 120 mg plus cetuximab | Intermittent regorafenib 160 mg plus cetuximab | |
|---|---|---|---|---|---|
| Regorafenib | |||||
| AUC(0–24) (mg hr/l) | Day −14 | (n = 5) 10.8 (88.6) | (n = 6) 20.8 (48.8) | (n = 8) 17.1 (55.0) | (n = 9) 28.5 (50.5) |
| C max (mg/l) | (n = 5) 0.7 (103) | (n = 6) 1.3 (46.9) | (n = 8) 1.2 (71.7) | (n = 9) 1.9 (58.3) | |
| T max 1 (hr) | (n = 5) 8.0 (4.0–24.0) | (n = 6) 8.0 (2.0–24.0) | (n = 8) 4.0 (2.0–7.5) | (n = 9) 2.3 (1.9–23.9) | |
| AUC(0–24) (mg hr/l) | Day 1 | (n = 4) 10.2 (114) | (n = 3) 21.7 (48.5) | (n = 2) NC | (n = 5) 30.1 (23.8) |
| C max (mg/l) | (n = 4) 0.8 (116) | (n = 4) 1.3 (98.3) | (n = 7) 1.1 (47.3) | (n = 9) 2.4 (44.3) | |
| T max 1 (hr) | (n = 4) 2.9 (2.0–23.6) | (n = 4) 7.9 (2.0–24.0) | (n = 7) 7.6 (2.0–22.0) | (n = 9) 2.0 (1.9–7.5) | |
| M‐2 | |||||
| AUC(0–last) (mg hr/l) | Day −14 | (n = 5) 2.6 (195) | (n = 6) 8.0 (96.1) | (n = 8) 4.8 (91.8) | (n = 9) 13.7 (85.8) |
| C max (mg/l) | (n = 5) 0.2 (208) | (n = 6) 0.5 (101) | (n = 8) 0.3 (100) | (n = 9) 0.8 (85.2) | |
| T max 1 (hr) | (n = 5) 8.0 (4.0–24.0) | (n = 6) 8.0 (8.0–24.0) | (n = 8) 7.5 (2.0–24.3) | (n = 9) 7.5 (3.9–23.8) | |
| AUC(0–last) (mg hr/l) | Day 1 | (n = 4) 3.7 (223) | (n = 4) 3.7 (158) | (n = 7) 2.8 (164) | (n = 9) 11.7 (100) |
| C max (mg/l) | (n = 4) 0.3 (168) | (n = 4) 0.3 (72.1) | (n = 7) 0.3 (57.9) | (n = 9) 1.3 (41.2) | |
| T max 1 (hr) | (n = 4) 3.9 (2.0–23.6) | (n = 4) 7.9 (2.0–24.0) | (n = 7) 7.6 (2.0–22.0) | (n = 9) 4.1 (2.0–8.0) | |
| M‐5 | |||||
| AUC(0–last) (mg hr/l) | Day −14 | (n = 3) 0.4 (28.5) | (n = 5) 0.8 (146) | (n = 7) 0.3 (126) | (n = 8) 1.4 (214) |
| C max (mg/l) | (n = 5) 0.01 (192) | (n = 6) 0.04 (221) | (n = 8) 0.02 (147) | (n = 9) 0.09 (180) | |
| T max 1 (hr) | (n = 5) 23.8 (7.5–24.0) | (n = 6) 24.0 (8.0–24.0) | (n = 8) 23.8 (22.6–24.5) | (n = 9) 23.8 (22.4–24.7) | |
| AUC(0–last) (mg hr/l) | Day 1 | (n = 3) 0.5 (214) | (n = 4) 0.3 (184) | (n = 6) 0.3 (259) | (n = 9) 1.3 (281) |
| C max (mg/l) | (n = 4) 0.02 (176) | (n = 4) 0.03 (72.7) | (n = 6) 0.03 (143) | (n = 9) 0.14 (127) | |
| T max 1 (hr) | (n = 4) 23.7 (23.5–24.5) | (n = 4) 23.9 (8.0–24.0) | (n = 6) 20.3 (7.6–23.7) | (n = 9) 8.0 (4.0–24.7) | |
1
Median (range).
Abbreviations: AUC, area under the concentration–time curve; C max, maximum observed drug concentration; CV, coefficient of variation; NC, not calculated; T max, time to reach maximum concentration in plasma.