Everolimus Concentration in Saliva to Predict Stomatitis: A Feasibility Study in Patients with Cancer

Laura Molenaar-Kuijsten, Remy B. Verheijen, Bart A.W. Jacobs, Bas Thijssen, Hilde Rosing, Thomas P.C. Dorlo, Jos H. Beijnen, Neeltje Steeghs, Alwin D.R. Huitema

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

BACKGROUND: Most patients with cancer treated with everolimus experience stomatitis, which seriously affects the quality of life. The salivary concentrations of everolimus may predict the incidence and severity of stomatitis. The authors aimed to examine whether it was feasible to quantify the everolimus concentration in saliva and subsequently use it to predict stomatitis. METHODS: Saliva and whole blood samples were taken from patients with cancer, who were treated with everolimus in the dosage of either 10 mg once a day or 5 mg twice a day. Everolimus concentrations in saliva samples were measured by liquid chromatography-tandem mass spectrometry. A published population pharmacokinetic model was extended with the everolimus concentration in saliva to assess any association between everolimus in the blood and saliva. Subsequently, the association between the occurrence of stomatitis and the everolimus concentration in saliva was studied. RESULTS: Eleven patients were included in this study; saliva samples were available from 10 patients, including 3 patients with low-grade stomatitis. Everolimus concentrations were more than 100-fold lower in saliva than in whole blood (accumulation ratio 0.00801 and relative standard error 32.5%). Interindividual variability (67.7%) and residual unexplained variability (84.0%) were high. The salivary concentration of everolimus tended to be higher in patients with stomatitis, 1 hour postdose ( P = 0.14). CONCLUSIONS: Quantification of the everolimus concentration in saliva was feasible and revealed a nonsignificant correlation between everolimus concentration in the saliva and the occurrence of stomatitis. If future research proves this relationship to be significant, the everolimus concentration in the saliva may be used as an early predictor of stomatitis without invasive sampling. Thereby, in patients with high salivary everolimus concentrations, precautions can be taken to decrease the incidence and severity of stomatitis.

Originele taal-2Engels
Pagina's (van-tot)520-526
Aantal pagina's7
TijdschriftTherapeutic Drug Monitoring
Volume44
Nummer van het tijdschrift4
DOI's
StatusGepubliceerd - 1 aug. 2022

Vingerafdruk

Duik in de onderzoeksthema's van 'Everolimus Concentration in Saliva to Predict Stomatitis: A Feasibility Study in Patients with Cancer'. Samen vormen ze een unieke vingerafdruk.

Citeer dit