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Clinical validation study of dried blood spot for determining everolimus concentration in patients with cancer

PURPOSE: Everolimus treatment is seriously hampered by its toxicity profile. As a relationship between everolimus exposure and effectiveness and toxicity has been established, early and ongoing concentration measurement can be key to individualize the dose and optimize treatment outcomes. Dried bloo...

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Autores principales: Willemsen, A. E. C. A. B., Knapen, L. M., de Beer, Y. M., Brüggemann, R. J. M., Croes, S., van Herpen, C. M. L., van Erp, N. P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849667/
https://www.ncbi.nlm.nih.gov/pubmed/29222715
http://dx.doi.org/10.1007/s00228-017-2394-0
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author Willemsen, A. E. C. A. B.
Knapen, L. M.
de Beer, Y. M.
Brüggemann, R. J. M.
Croes, S.
van Herpen, C. M. L.
van Erp, N. P.
author_facet Willemsen, A. E. C. A. B.
Knapen, L. M.
de Beer, Y. M.
Brüggemann, R. J. M.
Croes, S.
van Herpen, C. M. L.
van Erp, N. P.
author_sort Willemsen, A. E. C. A. B.
collection PubMed
description PURPOSE: Everolimus treatment is seriously hampered by its toxicity profile. As a relationship between everolimus exposure and effectiveness and toxicity has been established, early and ongoing concentration measurement can be key to individualize the dose and optimize treatment outcomes. Dried blood spot (DBS) facilitates sampling at a patients’ home and thereby eases dose individualization. The aim of this study is to determine the agreement and predictive performance of DBS compared to whole blood (WB) to measure everolimus concentrations in cancer patients. METHODS: Paired DBS and WB samples were collected in 22 cancer patients treated with everolimus and analyzed using UPLC-MS/MS. Bland-Altman and Passing-Bablok analysis were used to determine method agreement. Limits of clinical relevance were set at a difference of ± 25%, as this would lead to a different dosing advice. Using DBS concentration and Passing-Bablok regression analysis, WB concentrations were predicted. RESULTS: Samples of 20 patients were suitable for analysis. Bland-Altman analysis showed a mean ratio of everolimus WB to DBS concentrations of 0.90, with 95% of data points within limits of clinical relevance. Passing-Bablok regression of DBS compared to WB revealed no constant bias (intercept 0.02; 95% CI 0.93–1.35) and a small proportional bias (slope 0.89; 95% CI 0.76–0.99). Predicted concentrations showed low bias and imprecision and 90% of samples had an absolute percentage prediction error of < 20%. CONCLUSIONS: DBS is a valid method to determine everolimus concentrations in cancer patients. This can especially be of value for early recognition of over- or underexposure to enable dose adaptations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00228-017-2394-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-58496672018-03-21 Clinical validation study of dried blood spot for determining everolimus concentration in patients with cancer Willemsen, A. E. C. A. B. Knapen, L. M. de Beer, Y. M. Brüggemann, R. J. M. Croes, S. van Herpen, C. M. L. van Erp, N. P. Eur J Clin Pharmacol Pharmacokinetics and Disposition PURPOSE: Everolimus treatment is seriously hampered by its toxicity profile. As a relationship between everolimus exposure and effectiveness and toxicity has been established, early and ongoing concentration measurement can be key to individualize the dose and optimize treatment outcomes. Dried blood spot (DBS) facilitates sampling at a patients’ home and thereby eases dose individualization. The aim of this study is to determine the agreement and predictive performance of DBS compared to whole blood (WB) to measure everolimus concentrations in cancer patients. METHODS: Paired DBS and WB samples were collected in 22 cancer patients treated with everolimus and analyzed using UPLC-MS/MS. Bland-Altman and Passing-Bablok analysis were used to determine method agreement. Limits of clinical relevance were set at a difference of ± 25%, as this would lead to a different dosing advice. Using DBS concentration and Passing-Bablok regression analysis, WB concentrations were predicted. RESULTS: Samples of 20 patients were suitable for analysis. Bland-Altman analysis showed a mean ratio of everolimus WB to DBS concentrations of 0.90, with 95% of data points within limits of clinical relevance. Passing-Bablok regression of DBS compared to WB revealed no constant bias (intercept 0.02; 95% CI 0.93–1.35) and a small proportional bias (slope 0.89; 95% CI 0.76–0.99). Predicted concentrations showed low bias and imprecision and 90% of samples had an absolute percentage prediction error of < 20%. CONCLUSIONS: DBS is a valid method to determine everolimus concentrations in cancer patients. This can especially be of value for early recognition of over- or underexposure to enable dose adaptations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00228-017-2394-0) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2017-12-08 2018 /pmc/articles/PMC5849667/ /pubmed/29222715 http://dx.doi.org/10.1007/s00228-017-2394-0 Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Pharmacokinetics and Disposition
Willemsen, A. E. C. A. B.
Knapen, L. M.
de Beer, Y. M.
Brüggemann, R. J. M.
Croes, S.
van Herpen, C. M. L.
van Erp, N. P.
Clinical validation study of dried blood spot for determining everolimus concentration in patients with cancer
title Clinical validation study of dried blood spot for determining everolimus concentration in patients with cancer
title_full Clinical validation study of dried blood spot for determining everolimus concentration in patients with cancer
title_fullStr Clinical validation study of dried blood spot for determining everolimus concentration in patients with cancer
title_full_unstemmed Clinical validation study of dried blood spot for determining everolimus concentration in patients with cancer
title_short Clinical validation study of dried blood spot for determining everolimus concentration in patients with cancer
title_sort clinical validation study of dried blood spot for determining everolimus concentration in patients with cancer
topic Pharmacokinetics and Disposition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849667/
https://www.ncbi.nlm.nih.gov/pubmed/29222715
http://dx.doi.org/10.1007/s00228-017-2394-0
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