{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:23:02Z","timestamp":1790634182227,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,10]],"date-time":"2017-11-10T00:00:00Z","timestamp":1510272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Therapeutic drug monitoring (<jats:styled-content style=\"fixed-case\">TDM<\/jats:styled-content>) could be helpful in oral targeted therapies. Data are sparse to evaluate its impact on treatment management. This study aimed to determine a threshold value of plasma drug exposure associated with the occurrence of grade 3\u20134 toxicity, then the potential impact of <jats:styled-content style=\"fixed-case\">TDM<\/jats:styled-content> on clinical decision. Consecutive outpatients treated with sunitinib were prospectively monitored between days 21 and 28 of the first cycle, then monthly until disease progression. At each consultation, the composite <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>\u01ac,ss<\/jats:sub> (sunitinib\u00a0+\u00a0active metabolite <jats:styled-content style=\"fixed-case\">SU<\/jats:styled-content>12662) was assayed. The decisions taken during each consultation were matched with <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>\u01ac,ss<\/jats:sub> and compared to the decisional algorithm based on <jats:styled-content style=\"fixed-case\">TDM<\/jats:styled-content>. A total of 105 cancer patients and 288 consultations were matched with the closest <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>\u01ac,ss<\/jats:sub> measurement. The majority (60%) of the patients had metastatic renal clear\u2010cell carcinoma (m<jats:styled-content style=\"fixed-case\">RCC<\/jats:styled-content>). Fifty\u2010five (52%) patients experienced grade 3\u20134 toxicity. Multivariate analysis identified composite <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>\u01ac,ss<\/jats:sub> as a parameter independently associated with grade 3\u20134 toxicity (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). Using the <jats:styled-content style=\"fixed-case\">ROC<\/jats:styled-content> curve, the threshold value of composite <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>\u01ac,ss<\/jats:sub> predicting grade \u22653 toxicity was 2150\u00a0ng\/mL\/h (<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 95%, 0.6\u20130.79%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). At disease progression in patients with m<jats:styled-content style=\"fixed-case\">RCC<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> AUC<\/jats:styled-content><jats:sub>\u01ac,ss<\/jats:sub> tended to be lower than the one assayed during the first cycle (1678 vs. 2004\u00a0ng\/mL\/h, respectively, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.072). <jats:styled-content style=\"fixed-case\">TDM<\/jats:styled-content> could have changed the medical decision for sunitinib dosing in 30% of patients at the first cycle of treatment, and in 46% of the patients over the whole treatment course. <jats:styled-content style=\"fixed-case\">TDM<\/jats:styled-content> is routinely feasible and may both contribute to improve toxicity management and to identify sunitinib underexposure at the time of disease progression.<\/jats:p>","DOI":"10.1111\/fcp.12327","type":"journal-article","created":{"date-parts":[[2017,10,21]],"date-time":"2017-10-21T15:42:34Z","timestamp":1508600554000},"page":"98-107","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Drug monitoring of sunitinib in patients with advanced solid tumors: a monocentric observational French study"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5515-9180","authenticated-orcid":false,"given":"Luc","family":"Cabel","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Cochin Hospital, AP\u2010HP 27 rue du Faubourg Saint Jacques 75014 Paris France"},{"name":"Paris Descartes University, CARPEM Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Blanchet","sequence":"additional","affiliation":[{"name":"Department of Pharmacocokinetics and Pharmacochemistry Groupe de Pharmacologie Clinique Oncologique Cochin Hospital Paris 75014 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Thomas\u2010Schoemann","sequence":"additional","affiliation":[{"name":"Department of Pharmacocokinetics and Pharmacochemistry Groupe de Pharmacologie Clinique Oncologique Cochin Hospital Paris 75014 France"},{"name":"UMR8638 CNRS UFR de Pharmacie Universit\u00e9 Paris Descartes PRES Sorbonne Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Huillard","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Cochin Hospital, AP\u2010HP 27 rue du Faubourg Saint Jacques 75014 Paris France"},{"name":"Paris Descartes University, CARPEM Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Bellesoeur","sequence":"additional","affiliation":[{"name":"Department of Pharmacocokinetics and Pharmacochemistry Groupe de Pharmacologie Clinique Oncologique Cochin Hospital Paris 75014 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatole","family":"Cessot","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Cochin Hospital, AP\u2010HP 27 rue du Faubourg Saint Jacques 75014 Paris France"},{"name":"Paris Descartes University, CARPEM Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Giroux","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Cochin Hospital, AP\u2010HP 27 rue du Faubourg Saint Jacques 75014 Paris France"},{"name":"Paris Descartes University, CARPEM Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascaline","family":"Boudou\u2010Rouquette","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Cochin Hospital, AP\u2010HP 27 rue du Faubourg Saint Jacques 75014 Paris France"},{"name":"Paris Descartes University, CARPEM Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Coriat","sequence":"additional","affiliation":[{"name":"U1016 INSERM UMR 8104 CNRS UMR\u2010S1016 Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 Paris France"},{"name":"Department of Gastroenterology Cochin Hospital, AP\u2010HP Paris 75014 France"},{"name":"Paris Descartes University, CARPEM Paris 75006 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Vidal","sequence":"additional","affiliation":[{"name":"Department of Pharmacocokinetics and Pharmacochemistry Groupe de Pharmacologie Clinique Oncologique Cochin Hospital Paris 75014 France"},{"name":"UMR8638 CNRS UFR de Pharmacie Universit\u00e9 Paris Descartes PRES Sorbonne Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel E. 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