Quantitative and qualitative changes in platelet traits of sunitinib-treated patients with renal cell carcinoma in relation to circulating sunitinib levels: a proof-of-concept study.

Autor: Tullemans BME; Cardiovascular Research Institute Maastricht, Department of Biochemistry, Maastricht University, Maastricht, The Netherlands., Brouns SLN; Cardiovascular Research Institute Maastricht, Department of Biochemistry, Maastricht University, Maastricht, The Netherlands., Swieringa F; Cardiovascular Research Institute Maastricht, Department of Biochemistry, Maastricht University, Maastricht, The Netherlands.; Synapse Research Institute, Maastricht, The Netherlands., Sabrkhany S; Cardiovascular Research Institute Maastricht, Department of Physiology, Maastricht University, Maastricht, The Netherlands., van den Berkmortel FWPJ; Department of Medical Oncology, Zuyderland Medical Centre, Sittard-Geleen, The Netherlands., Peters NAJB; Department of Internal Medicine, Sint Jans Gasthuis, Weert, The Netherlands., de Bruijn P; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Centre, Rotterdam, The Netherlands., Koolen SLW; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Centre, Rotterdam, The Netherlands.; Department of Pharmacy, Erasmus University Medical Centre, Rotterdam, The Netherlands., Heemskerk JWM; Cardiovascular Research Institute Maastricht, Department of Biochemistry, Maastricht University, Maastricht, The Netherlands.; Synapse Research Institute, Maastricht, The Netherlands., Aarts MJB; Department of Medical Oncology, Maastricht University Medical Centre+, Maastricht, The Netherlands., Kuijpers MJE; Cardiovascular Research Institute Maastricht, Department of Biochemistry, Maastricht University, Maastricht, The Netherlands. Marijke.Kuijpers@maastrichtuniversity.nl.; Thrombosis Expertise Centre, Heart and Vascular Centre, Maastricht University Medical Centre, Maastricht, The Netherlands. Marijke.Kuijpers@maastrichtuniversity.nl.
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2022 Jun 13; Vol. 22 (1), pp. 653. Date of Electronic Publication: 2022 Jun 13.
DOI: 10.1186/s12885-022-09676-0
Abstrakt: Background: Tyrosine kinase inhibitors (TKIs), such as sunitinib, are used for cancer treatment, but may also affect platelet count and function with possible hemostatic consequences. Here, we investigated whether patient treatment with the TKI sunitinib affected quantitative and qualitative platelet traits as a function of the sunitinib level and the occurrence of bleeding.
Methods: Blood was collected from 20 metastatic renal cell carcinoma (mRCC) patients before treatment, and at 2 weeks, 4 weeks and 3 months after sunitinib administration. We measured blood cell counts, platelet aggregation, and concentrations of sunitinib as well as its N-desethyl metabolite in plasma, serum and isolated platelets. Progression of disease (PD) and bleeding were monitored after 3 months.
Results: In sunitinib-treated mRCC patients, concentrations of (N-desethyl-)sunitinib in plasma and serum were highly correlated. In the patients' platelets the active metabolite levels were relatively increased as compared to sunitinib. On average, a sustained reduction in platelet count was observed on-treatment, which was significantly related to the inhibitor levels in plasma/serum. Principal component and correlational analysis showed that the (N-desethyl-)sunitinib levels in plasma/serum were linked to a reduction in both platelet count and collagen-induced platelet aggregation. The reduced aggregation associated in part with reported bleeding, but did not correlate to PD.
Conclusion: The sunitinib-induced reduction in quantitative and qualitative platelet traits may reflect the effective sunitinib levels in the patient. These novel results may serve as a proof-of-principle for other TKI-related drugs, where both platelet count and functions are affected, which could be used for therapeutic drug monitoring.
(© 2022. The Author(s).)
Databáze: MEDLINE
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