{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:23:06Z","timestamp":1791361386853,"version":"4.3.1"},"reference-count":24,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,8,20]],"date-time":"2018-08-20T00:00:00Z","timestamp":1534723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003769","name":"Eisai","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Urology"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>To assess the tolerability, safety, pharmacokinetics and antitumor activities of lenvatinib, an oral inhibitor of multiple receptor tyrosine kinases, in combination with everolimus, an inhibitor of mammalian target of rapamycin, in Japanese patients with advanced or metastatic renal cell carcinoma after disease progression with vascular endothelial growth factor\u2010targeted therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Lenvatinib 18\u00a0mg and everolimus 5\u00a0mg once daily were administered on 28\u2010day continuous cycles until disease progression or unacceptable toxicity. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events version 4.03, and tumor response was assessed according to the Response Evaluation Criteria in Solid Tumor version 1.1. Pharmacokinetics sampling was carried out during the first cycle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seven patients with clear cell renal cell carcinoma received this combination treatment. Dose\u2010limiting toxicity was not observed. The most commonly observed adverse events were thrombocytopenia and decreased appetite (100%), followed by hypertriglyceridaemia and palmar\u2010plantar erythrodysesthesia syndrome (86%). The most common grade\u00a03 adverse event was lymphopenia (43%). No grade\u00a04 or 5 adverse events occurred. The steady\u2010state mean areas under the concentration\u2013time curves of lenvatinib and everolimus were 3220 and 401\u00a0ng\u00b7h\/mL, respectively. Five patients (71%) had partial response, and one (14%) had stable disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Lenvatinib 18\u00a0mg and everolimus 5\u00a0mg once daily are well tolerated and manageable, and their combined administration has no significant effect on either drug's pharmacokinetics. 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