{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:23:59Z","timestamp":1787664239964,"version":"build-2736575974"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005405","name":"Ritsumeikan University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005405","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Clin Oncol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Severe adverse events frequently occur in patients treated with cabozantinib in routine clinical care, and suboptimal responses to cabozantinib are seen in certain patients. In this prospective and observational clinical study, we investigated cabozantinib concentration\u2013response and concentration-toxicity relationships.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>We examined twelve patients with renal cell carcinoma treated with cabozantinib monotherapy between March 2021 and March 2024. We assessed the association of serum trough cabozantinib concentrations with the best tumor shrinkage rates. We also evaluated the association between trough cabozantinib concentrations and occurrence of adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      There was a significant positive correlation between the concentrations of cabozantinib and the best tumor shrinkage rates (\n                      <jats:italic>R<\/jats:italic>\n                      \u2009=\u20090.64,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.026). The trough cabozantinib concentration was significantly lower in patients without adverse events than patients with grade\u2009\u2265\u20091 adverse events, such as increased aspartate aminotransferase (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003), hand-foot syndrome (HFS) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.025), increased alanine aminotransferase (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.008), hoarseness (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.026), and dysgeusia (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Furthermore, there were significant differences in the trough cabozantinib concentrations between patients with grade\u2009\u2264\u20091 and patients with grade\u2009\u2265\u20092 adverse events, including hypertension (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.019) and HFS (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.038).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In patients with renal cell carcinoma, serum cabozantinib concentrations were correlated with maximum tumor shrinkage rates in a clinical setting. This study also suggested that the occurrence of adverse events, such as HFS and hypertension, is associated with the serum concentrations of cabozantinib.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10147-026-03112-0","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T14:41:28Z","timestamp":1783176088000},"page":"2016-2024","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Relationships of serum cabozantinib concentration with tumor response and adverse events in treatment of advanced renal cell carcinoma: observational exploratory prospective study"],"prefix":"10.1007","volume":"31","author":[{"given":"Yutaro","family":"Doke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Noda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuto","family":"Kusaba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiki","family":"Hira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshito","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Kageyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Terada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4079-707X","authenticated-orcid":false,"given":"Shin-ya","family":"Morita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,4]]},"reference":[{"key":"3112_CR1","doi-asserted-by":"publisher","first-page":"2298","DOI":"10.1158\/1535-7163.MCT-11-0264","volume":"10","author":"FM Yakes","year":"2011","unstructured":"Yakes FM, Chen J, Tan J et al (2011) Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. 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