Table 1.
Pharmacokinetic parameters of regorafenib (16 mg/kg, p.o.) with and without RT 2 and 9 Gy.
| Parameter | AUC0-T | Cmax | Tmax | t½ | Cl | Vss | MRT |
|---|---|---|---|---|---|---|---|
| Unit | min mg/mL | mg/mL | min | min | mL/min/kg | mL/kg | min |
| Regorafenib 16 mg/kg × 1 d |
226.8 ± 122.7 | 1.45 ± 0.77 | 190 ± 68 | 942.3 ± 535.1 | 8.18 ± 3.06 | 12641.9 ± 6928.9 | 1483 ± 1066 |
| Regorafenib 16 mg/kg × 3d | 849.6 ± 317.3 a | 4.19 ± 1.53 | 90 ± 63 | 550 ± 146 | 4.21 ± 1.82 | 3604.5 ± 951.1 | 823 ± 341 |
| RT2 Gy × 1 f’x with regorafenib 16 mg/kg × 1d |
152.2 ± 143.5 | 0.92 ± 0.85 | 165 ± 59 | 409 ± 150 | 16.6 ± 7.21 | 21606.9 ± 20731.8 | 651 ± 215 |
| RT2 Gy × 1 f’x followed by regorafenib 16 mg/kg × 1 d |
641.8 ± 305.1 b,e | 3.63 ± 1.76 | 180 ± 63 | 346 ± 93 | 6.19 ± 0.35 | 3081.4 ± 773.1 | 553 ± 116 |
| RT2 Gy × 3 f’x with regorafenib 16 mg/kg × 3 d |
223.0 ± 134.0 d,j | 1.24 ± 0.79l | 125 ± 58 | 372 ± 152 | 23.20 ± 9.45 n | 12759.6 ± 8467.4 p | 584 ± 186 |
| RT2 Gy × 3 f’x followed by regorafenib 16 mg/kg × 3 d |
673.7 ± 224.1 c,f | 3.55 ± 1.08 | 100 ± 24 | 920 ± 956 | 8.56 ± 7.21 | 4156.0 ± 1959.9 | 1370 ± 1365 |
| RT9 Gy × 1 f’x
with regorafenib 16 mg/kg × 1 d |
147.5 ± 187.0 | 0.83 ± 0.99 | 155 ± 84 | 654 ± 445 | 34.6 ± 25.3 | 30999.0 ± 34618.0 | 976.3 ± 639.4 |
| RT9 Gy × 1 f’x followed by regorafenib 16 mg/kg × 1 d |
711.4 ± 392.8 g,k | 4.32 ± 2.71 | 155 ± 29 | 608 ± 210 | 3.3 ± 4.3 | 2898.8 ± 4123.7 | 935.1 ± 320.9 |
| RT9 Gy × 3 f’x with regorafenib 16 mg/kg × 3 d |
260.0 ± 110.7 i | 1.39 ± 0.53 m | 98 ± 81 | 662 ± 598 | 19.0 ± 11.7 o | 11564.4 ± 3361.0 q | 983.1 ± 857.7 |
| RT9 Gy × 3 f’x followed by regorafenib 16 mg/kg × 3 d |
460.6 ± 220.5 h,j | 2.49 ± 1.49 | 110 ± 78 | 571 ± 323 | 11.4 ± 4.5 | 7960.3 ± 3023.5 r | 860.7 ± 467.9 |
a Regorafenib × 1 d vs. regorafenib × 3 d, p = 0.001. b RT2 Gy × 1 f’x followed by regorafenib vs. regorafenib × 1 d, p = 0.011. c RT2 Gy × 3 f’x followed by regorafenib × 3 d vs. regorafenib × 1 d, p = 0.002. d RT2 Gy × 3 f’x concurrent with regorafenib × 3 d vs. regorafenib × 3 d, p = 0.001. e RT2 Gy × 1 f’x concurrent with regorafenib × 1 d vs. RT2 Gy x 1 f’x followed by regorafenib × 1 d, p = 0.005. f RT2 Gy × 3 f’x concurrent with regorafenib × 3 d vs. RT2 Gy × 3 f’x followed by regorafenib × 3 d, p = 0.002. g RT9 Gy × 1 f’x followed by regorafenib × 1 d vs. regorafenib × 1 d, p = 0.016. h RT9 Gy × 1 f’x followed by regorafenib × 3 d vs. regorafenib × 1 d, p = 0.047. i RT9 Gy × 3 f’x concurrent with regorafenib × 3 d vs. regorafenib × 3 d, p = 0.001. j RT9 Gy × 3 f’x followed by regorafenib × 3 d vs. regorafenib × 3 d, p = 0.033. k RT9 Gy × 1 f’x concurrent with regorafenib × 1 d vs. RT9Gy × 1 f’x followed by regorafenib × 1 d, p = 0.010. l RT2 Gy × 3 f’x concurrent with regorafenib × 3 d vs. regorafenib × 3 d, p = 0.002. m RT9 Gy × 3 f’x concurrent with regorafenib × 3 d vs. regorafenib × 3 d, p = 0.001. n RT2 Gy × 3 f’x concurrent with regorafenib × 3 d vs. regorafenib × 3 d, p = 0.01. o RT9 Gy × 3 f’x concurrent with regorafenib × 3 d vs. regorafenib × 3 d, p = 0.05. p RT2 Gy × 3 f’x concurrent with regorafenib × 3 d vs. regorafenib × 3 d, p = 0.03. q RT9 Gy × 3 f’x concurrent with regorafenib × 3 d vs. regorafenib × 3 d, p = 0.001. r RT9 Gy × 3 f’x followed by regorafenib × 3 d vs. regorafenib × 3 d, p = 0.01.