{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:42:59Z","timestamp":1791571379720,"version":"4.3.4"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T00:00:00Z","timestamp":1590451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["11575"],"award-info":[{"award-number":["11575"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Sunitinib is an oral tyrosine kinase inhibitor approved for the treatment of renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST). Because of the large interpatient pharmacokinetic variability and established exposure\u2010response and exposure\u2010toxicity relationships in clinical trial patients, therapeutic drug monitoring (TDM) seems promising for optimizing sunitinib exposure. We aimed to investigate the relationship between sunitinib exposure and treatment outcome in a real\u2010world patient cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a retrospective observational cohort study in 53 patients with metastatic RCC and 18 patients with metastatic GIST treated with sunitinib and receiving TDM\u2010guided dosing. Time on treatment \u2013 as a surrogate for progression\u2010free survival \u2013 in patients who achieved adequate sunitinib exposure was compared with patients who did not. Additionaly, the median sunitinib exposure was compared in patients with or without sunitinib\u2010induced toxicity leading to dose reduction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The median time on treatment in patients with RCC who achieved adequate sunitinib exposure (n = 39) was 32 weeks, compared to 15 weeks in patients who did not achieve adequate sunitinib exposure (n = 12) (<jats:italic>P<\/jats:italic> = 0.244). In 29 patients (41%) with toxicity leading to dose reduction, sunitinib sum plasma trough concentration (<jats:italic>C<\/jats:italic><jats:sub>trough<\/jats:sub>) until dose reduction was significantly higher compared to patients without toxicity leading to dose reduction (median 60 ng\/mL <jats:italic>vs<\/jats:italic> 44 ng\/mL; <jats:italic>P<\/jats:italic> &lt; 0.001) and reduced to comparable levels after dose reduction (44 ng\/mL; <jats:italic>P<\/jats:italic> = 0.488).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In our real\u2010world patient cohort, patients with sunitinib\u2010induced toxicity requiring dose reduction had significantly higher sunitinib exposure compared to patients without toxicity. The threshold for toxicity, however, was lower compared to that previously described in clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14332","type":"journal-article","created":{"date-parts":[[2020,5,2]],"date-time":"2020-05-02T03:58:40Z","timestamp":1588391920000},"page":"326-335","source":"Crossref","is-referenced-by-count":28,"title":["The relationship between sunitinib exposure and both efficacy and toxicity in real\u2010world patients with renal cell carcinoma and gastrointestinal stromal tumour"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3512-4671","authenticated-orcid":false,"given":"Kim","family":"Westerdijk","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Radboud Institute for Health Sciences Radboud University Medical Center  Nijmegen Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie D.","family":"Krens","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Radboud Institute for Health Sciences Radboud University Medical Center  Nijmegen Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winette T.A.","family":"van der Graaf","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Radboud Institute for Health Sciences Radboud University Medical Center  Nijmegen Netherlands"},{"name":"Department of Medical Oncology Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital  Amsterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasja F.","family":"Mulder","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Radboud Institute for Health Sciences Radboud University Medical Center  Nijmegen Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla M.L.","family":"van Herpen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Radboud Institute for Health Sciences Radboud University Medical Center  Nijmegen Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tineke","family":"Smilde","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Jeroen Bosch Hospital, \u2018s Hertogenbosch  Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1553-178X","authenticated-orcid":false,"given":"Nielka P.","family":"van Erp","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Radboud Institute for Health Sciences Radboud University Medical Center  Nijmegen Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid M.E.","family":"Desar","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Radboud Institute for Health Sciences Radboud University Medical Center  Nijmegen Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1303989"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-3005"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1003825"},{"key":"e_1_2_10_5_1","unstructured":"Committee for Medicinal Products for Human Use (CHMP) EMA. 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