Oral rigosertib plasma PK parameters | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
70 mg | 140 mg | 280 mg | 560 mg | 700 mg | ||||||
Parameter | Day 1 (n = 3; mean ± SD) | Day 21 (n = 3; mean ± SD) | Day 1 (n = 4; mean ± SD) | Day 21 (n = 4; mean ± SD) | Day 1 (n = 5; mean ± SD) | Day 21 (n = 3; mean ± SD) | Day 1 (n = 32; mean ± SD) | Day 21 (n = 24; mean ± SD) | Day 1 (n = 7; mean ± SD) | Day 21 (n = 2; mean ± SD) |
C_{max} (μg/mL) | 0.40 ± 0.29 | NA | 0.20 ± 0.07 | 0.43 ± 0.26 | 1.84 ± 1.31 | 0.73 ± 0.44 | 4.04 ± 2.97 | 2.54 ± 2.35 | 5.93 ± 4.74 | 2.34 ± 1.28 |
P = 0.0463^{a} | ||||||||||
AUC_{0-∞} (μg*h/mL) | 1.52 ± 1.36 | NA | 3.49 ± 5.25 | 4.59 ± 4.85 | 4.93 ± 4.06 | 2.61 ± 1.23 | 9.32 ± 6.92 | 6.99 ± 5.88 | 19.58 ± 22.95 | 4.96 ± 1.71 |
P = 0.1898^{a} | ||||||||||
T_{max} (h) | 1.17 ± 0.29 | NA | 1.13 ± 0.25 | 0.88 ± 0.25 | 1.00 ± 0.35 | 0.83 ± 0.58 | 1.02 ± 0.32 | 1.08 ± 0.41 | 1.14 ± 0.48 | 1.25 ± 0.35 |
P = 0.5409^{a} | ||||||||||
V_{ss}/F (L) | 439.4 ± 512.8 | NA | 1101.8 ± 424.4 | 787.9 ± 415.4 | 498.5 ± 469.3 | 1061.4 ± 603.4 | 314.9 ± 285.2 | 573.8 ± 498.5 | 241.7 ± 211.8 | 472.8 ± 137.5 |
P = 0.0173^{a} | ||||||||||
CL/F (L/h) | 71.54 ± 42.87 | NA | 171.29 ± 155.74 | 55.64 ± 36.62 | 122.84 ± 123.67 | 127.45 ± 66.13 | 93.28 ± 58.24 | 116.33 ± 56.32 | 64.62 ± 34.70 | 149.9 ± 51.79 |
P = 0.1430^{a} | ||||||||||
T_{1/2} (h) | 3.34 ± 2.40 | NA | 21.56 ± 36.39 | 25.69 ± 38.29 | 2.81 ± 0.77 | 5.29 ± 1.09 | 2.42 ± 1.10 | 4.03 ± 2.92 | 3.09 ± 2.18 | 1.99 ± 0.47 |
P = 0.0059^{a} |
NOTE: Individual patients underwent PK testing after oral dosing on days 1 and 21 of cycle 1. For patients treated at the RP2D of rigosertib (560 mg twice daily), C_{max} was significantly lower at steady-state on day 21 than on day 1.
Abbreviations: AUC_{0-∞}, area under the curve determined from time zero extrapolated to infinity; C_{max}, maximal concentration; CL/F, clearance T_{max} (h), time of peak concentration; T_{1/2} (h), terminal elimination phase half-life; V_{ss}/F (L), apparent volume of distribution at steady state.
↵^{a}Unpaired t test at 95% confidence interval.