A simple and rapid LC-MS/MS method for therapeutic drug monitoring of cetuximab: a GPCO-UNICANCER proof of concept study in head-and-neck cancer patients
Abstract Administration of first-in-class anti-EGFR monoclonal antibody cetuximab is contingent upon extensive pharmacogenomic testing. However in addition to tumor genomics, drug exposure levels could play a critical, yet largely underestimated role, because several reports have demonstrated that c...
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Nature Portfolio
2017
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oai:doaj.org-article:59b1810b3de1458f856d8917cd3a443c2021-12-02T11:52:57ZA simple and rapid LC-MS/MS method for therapeutic drug monitoring of cetuximab: a GPCO-UNICANCER proof of concept study in head-and-neck cancer patients10.1038/s41598-017-02821-x2045-2322https://doaj.org/article/59b1810b3de1458f856d8917cd3a443c2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02821-xhttps://doaj.org/toc/2045-2322Abstract Administration of first-in-class anti-EGFR monoclonal antibody cetuximab is contingent upon extensive pharmacogenomic testing. However in addition to tumor genomics, drug exposure levels could play a critical, yet largely underestimated role, because several reports have demonstrated that cetuximab pharmacokinetic parameters, in particular clearance values, were associated with survival in patients. Here, we have developed an original bioanalytical method based upon the use of LC-MS/MS technology and a simplified sample preparation procedure to assay cetuximab in plasma samples from patients, thus meeting the requirements of standard Therapeutic Drug Monitoring in routine clinical practice. When tested prospectively in a pilot study in 25 head-and-neck cancer patients, this method showed that patients with clinical benefit had cetixumab residual concentrations higher than non-responding patients (i.e., 49 ± 16.3 µg/ml VS. 25.8 ± 17 µg/ml, p < 0.01 t test). Further ROC analysis showed that 33.8 µg/ml was the Cmin threshold predictive of response with an acceptable sensitivity (87%) and specificity (78%). Mass spectrometry-based therapeutic drug monitoring of cetuximab in head-and-neck cancer patients could therefore help to rapidly predict cetuximab efficacy and to adapt dosing if required.François BecherJoseph CiccoliniDiane-Charlotte ImbsClémence MarinClaire FournelCharlotte DupuisNicolas FakhryBertrand PourroyAurélie GhettasAlain PruvostChristophe JunotFlorence DuffaudBruno LacarelleSebastien SalasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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DOAJ |
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DOAJ |
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| topic |
Medicine R Science Q |
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Medicine R Science Q François Becher Joseph Ciccolini Diane-Charlotte Imbs Clémence Marin Claire Fournel Charlotte Dupuis Nicolas Fakhry Bertrand Pourroy Aurélie Ghettas Alain Pruvost Christophe Junot Florence Duffaud Bruno Lacarelle Sebastien Salas A simple and rapid LC-MS/MS method for therapeutic drug monitoring of cetuximab: a GPCO-UNICANCER proof of concept study in head-and-neck cancer patients |
| description |
Abstract Administration of first-in-class anti-EGFR monoclonal antibody cetuximab is contingent upon extensive pharmacogenomic testing. However in addition to tumor genomics, drug exposure levels could play a critical, yet largely underestimated role, because several reports have demonstrated that cetuximab pharmacokinetic parameters, in particular clearance values, were associated with survival in patients. Here, we have developed an original bioanalytical method based upon the use of LC-MS/MS technology and a simplified sample preparation procedure to assay cetuximab in plasma samples from patients, thus meeting the requirements of standard Therapeutic Drug Monitoring in routine clinical practice. When tested prospectively in a pilot study in 25 head-and-neck cancer patients, this method showed that patients with clinical benefit had cetixumab residual concentrations higher than non-responding patients (i.e., 49 ± 16.3 µg/ml VS. 25.8 ± 17 µg/ml, p < 0.01 t test). Further ROC analysis showed that 33.8 µg/ml was the Cmin threshold predictive of response with an acceptable sensitivity (87%) and specificity (78%). Mass spectrometry-based therapeutic drug monitoring of cetuximab in head-and-neck cancer patients could therefore help to rapidly predict cetuximab efficacy and to adapt dosing if required. |
| format |
article |
| author |
François Becher Joseph Ciccolini Diane-Charlotte Imbs Clémence Marin Claire Fournel Charlotte Dupuis Nicolas Fakhry Bertrand Pourroy Aurélie Ghettas Alain Pruvost Christophe Junot Florence Duffaud Bruno Lacarelle Sebastien Salas |
| author_facet |
François Becher Joseph Ciccolini Diane-Charlotte Imbs Clémence Marin Claire Fournel Charlotte Dupuis Nicolas Fakhry Bertrand Pourroy Aurélie Ghettas Alain Pruvost Christophe Junot Florence Duffaud Bruno Lacarelle Sebastien Salas |
| author_sort |
François Becher |
| title |
A simple and rapid LC-MS/MS method for therapeutic drug monitoring of cetuximab: a GPCO-UNICANCER proof of concept study in head-and-neck cancer patients |
| title_short |
A simple and rapid LC-MS/MS method for therapeutic drug monitoring of cetuximab: a GPCO-UNICANCER proof of concept study in head-and-neck cancer patients |
| title_full |
A simple and rapid LC-MS/MS method for therapeutic drug monitoring of cetuximab: a GPCO-UNICANCER proof of concept study in head-and-neck cancer patients |
| title_fullStr |
A simple and rapid LC-MS/MS method for therapeutic drug monitoring of cetuximab: a GPCO-UNICANCER proof of concept study in head-and-neck cancer patients |
| title_full_unstemmed |
A simple and rapid LC-MS/MS method for therapeutic drug monitoring of cetuximab: a GPCO-UNICANCER proof of concept study in head-and-neck cancer patients |
| title_sort |
simple and rapid lc-ms/ms method for therapeutic drug monitoring of cetuximab: a gpco-unicancer proof of concept study in head-and-neck cancer patients |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/59b1810b3de1458f856d8917cd3a443c |
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