Higher systemic exposure to unbound active metabolites of regorafenib is associated with short progression-free survival in colorectal cancer patients.

We examined area under the unbound plasma concentration-time curve (AUCu) to these compounds to establish pharmacokinetic bases for individualized dosing-strategies. The plasma protein binding of M-2 and M-5 was approximately 10-fold lower than that of regorafenib, whereas AUCu values for active metabolites on both days 1 and 15 were significantly higher than that of regorafenib. Patients with higher AUCu values of M-2 or M-5 on day 1 showed significantly shorter progression-free survival than others, likely due, at least in part to treatment discontinuation as a result of adverse events, especially occurred during first cycle.
PMID: 32034953 [PubMed - as supplied by publisher]

Source: Clinical Colorectal Cancer - February 7, 2020 Category: Cancer & Oncology Authors: Kubota Y, Fujita KI, Takahashi T, Sunakawa Y, Ishida H, Hamada K, Ichikawa W, Tsunoda T, Shimada K, Masuo Y, Kato Y, Sasaki Y Tags: Clin Pharmacol Ther Source Type: research