Feasibility of therapeutic drug monitoring of sorafenib in patients with liver or thyroid cancer.

We included patients who started on sorafenib (between October 2017 and June 2020) at the recommended dose of 400 mg BID or with a step-up dosing schedule. Plasma trough levels (C_trough) were measured at pre-specified time-points. Increasing the dose was advised if C_trough was below the target of 3750 ng/mL and toxicity was manageable.

TDM for sorafenib is not of added value in daily clinical practice. In most cases, toxicity restricts the possibility of dose escalations.

A total of 150 samples from 36 patients were collected. Thirty patients (83 %) had a C_trough below the prespecified target concentration at a certain time point during treatment. Toxicity from sorafenib hampered dosing according to target C_trough in almost half of the patients. In 11 patients, dosing was adjusted based on C_trough. In three patients, this resulted in an adequate C_trough without additional toxicity four weeks after the dose increase. In the remaining eight patients, dose adjustment based on C_trough did not result in a C_trough above the target or caused excessive toxicity.

Sorafenib is a tyrosine-kinase inhibitor approved for the treatment of renal cell carcinoma, hepatocellular carcinoma, thyroid carcinoma, and desmoid fibromatosis. As high inter-individual variability exists in exposure, there is a scientific rationale to pursue therapeutic drug monitoring (TDM). We investigated the feasibility of TDM in patients on sorafenib and tried to identify sub-groups in whom pharmacokinetically (PK) guided-dosing might be of added value.