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. 2023 Aug 22;29(21):4341–4351. doi: 10.1158/1078-0432.CCR-23-0257

Figure 3.

Figure 3. BSA-normalized exposure AUC (left) and clearance of regorafenib (right) and pharmacokinetics parameters of regorafenib administered with VI (bottom right table). The closed green circles denote concomitant dosing—lower BSA-normalized clearance in one of the two patients in the concomitant dosing cohort is not likely to be due to a drug–drug interaction, as irinotecan, SN-38, and vincristine do not inhibit CYP3A4. Boxplots show the median (solid line at center of box) and its approximate 95% confidence interval (gray area), the interquartile range (box), 1.5× interquartile range (whiskers), and outliers (closed circles). *An additional two patients received concomitant regorafenib 72 mg/m2 (AUC(0–24)md range, 62.8–114.0 mg•h/L and t½eff,md range, 50.3–64.3 hours). Box plots for different doses of regorafenib monotherapy (blue boxes) are shown for comparison. AUC(0–24)md, area under the plasma concentration–time curve over a dosing interval of 24 hours after multiple dosing; BSA, body surface area; CV, coefficient of variation; t½eff,md, effective half-life after multiple dosing; VI, vincristine and irinotecan.

BSA-normalized exposure AUC (left) and clearance of regorafenib (right) and pharmacokinetics parameters of regorafenib administered with VI (bottom right table). The closed green circles denote concomitant dosing—lower BSA-normalized clearance in one of the two patients in the concomitant dosing cohort is not likely to be due to a drug–drug interaction, as irinotecan, SN-38, and vincristine do not inhibit CYP3A4. Boxplots show the median (solid line at center of box) and its approximate 95% confidence interval (gray area), the interquartile range (box), 1.5× interquartile range (whiskers), and outliers (closed circles). *An additional two patients received concomitant regorafenib 72 mg/m2 (AUC(0–24)md range, 62.8–114.0 mg•h/L and t½eff,md range, 50.3–64.3 hours). Box plots for different doses of regorafenib monotherapy (blue boxes) are shown for comparison. AUC(0–24)md, area under the plasma concentration–time curve over a dosing interval of 24 hours after multiple dosing; BSA, body surface area; CV, coefficient of variation; t½eff,md, effective half-life after multiple dosing; VI, vincristine and irinotecan.