TY - JOUR
T1 - Feasibility of therapeutic drug monitoring of sorafenib in patients with liver or thyroid cancer
AU - Guchelaar, Niels A.D.
AU - van Eerden, Ruben A.G.
AU - On behalf of the Dutch Pharmacology Oncology Group
AU - Groenland, Stefanie L.
AU - Doorn, Leni van
AU - Desar, Ingrid M.E.
AU - Eskens, Ferry A.L.M.
AU - Steeghs, Neeltje
AU - van Erp, Nielka P.
AU - Huitema, Alwin D.R.
AU - Mathijssen, Ron H.J.
AU - Koolen, Stijn L.W.
N1 - Funding Information:
This work was supported by unrestricted research grants from Ipsen ; Merck ; Novartis ; Pfizer ; and Roche . They had no involvement in any other aspect of this study.
Publisher Copyright:
© 2022 The Authors
PY - 2022/9
Y1 - 2022/9
N2 - Introduction: 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. Methods: 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 (Ctrough) were measured at pre-specified time-points. Increasing the dose was advised if Ctrough was below the target of 3750 ng/mL and toxicity was manageable. Results: A total of 150 samples from 36 patients were collected. Thirty patients (83 %) had a Ctrough below the prespecified target concentration at a certain time point during treatment. Toxicity from sorafenib hampered dosing according to target Ctrough in almost half of the patients. In 11 patients, dosing was adjusted based on Ctrough. In three patients, this resulted in an adequate Ctrough without additional toxicity four weeks after the dose increase. In the remaining eight patients, dose adjustment based on Ctrough did not result in a Ctrough above the target or caused excessive toxicity. Conclusions: TDM for sorafenib is not of added value in daily clinical practice. In most cases, toxicity restricts the possibility of dose escalations.
AB - Introduction: 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. Methods: 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 (Ctrough) were measured at pre-specified time-points. Increasing the dose was advised if Ctrough was below the target of 3750 ng/mL and toxicity was manageable. Results: A total of 150 samples from 36 patients were collected. Thirty patients (83 %) had a Ctrough below the prespecified target concentration at a certain time point during treatment. Toxicity from sorafenib hampered dosing according to target Ctrough in almost half of the patients. In 11 patients, dosing was adjusted based on Ctrough. In three patients, this resulted in an adequate Ctrough without additional toxicity four weeks after the dose increase. In the remaining eight patients, dose adjustment based on Ctrough did not result in a Ctrough above the target or caused excessive toxicity. Conclusions: TDM for sorafenib is not of added value in daily clinical practice. In most cases, toxicity restricts the possibility of dose escalations.
UR - http://www.scopus.com/inward/record.url?scp=85133917389&partnerID=8YFLogxK
U2 - 10.1016/j.biopha.2022.113393
DO - 10.1016/j.biopha.2022.113393
M3 - Article
C2 - 35834987
AN - SCOPUS:85133917389
SN - 0753-3322
VL - 153
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
M1 - 113393
ER -
