{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T23:00:57Z","timestamp":1778799657315,"version":"3.51.4"},"reference-count":57,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2017,8,10]],"date-time":"2017-08-10T00:00:00Z","timestamp":1502323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multikinase inhibitors (MKI) and mammalian target of rapamycin (mTOR) inhibitors prolong progression-free (PFS) and overall survival (OS) in the treatment of metastatic renal cell carcinoma (mRCC) by reducing angiogenesis and tumor growth. In this regard, the MKI lenvatinib and the mTOR inhibitor everolimus proved effective when applied alone, but more effective when they were administered combined. Recently, both drugs were included in clinical trials, resulting in international clinical guidelines for the treatment of mRCC. In May 2016, lenvatinib was approved by the American Food and Drug Administration (FDA) for the use in combination with everolimus, as treatment of advanced renal cell carcinoma following one prior antiangiogenic therapy. A major problem of treating mRCC with lenvatinib and everolimus is the serious adverse event (AE) of arterial hypertension. During the treatment with everolimus and lenvatinib combined, 42% of the patients developed hypertension, while 10% of the patients treated with everolimus alone and 48% of the of the lenvatinib only treated patients developed hypertension. Lenvatinib carries warnings and precautions for hypertension, cardiac failure, and other adverse events. Therefore, careful monitoring of the patients is necessary.<\/jats:p>","DOI":"10.3390\/ijms18081736","type":"journal-article","created":{"date-parts":[[2017,8,10]],"date-time":"2017-08-10T10:34:35Z","timestamp":1502361275000},"page":"1736","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Hypertension Caused by Lenvatinib and Everolimus in the Treatment of Metastatic Renal Cell Carcinoma"],"prefix":"10.3390","volume":"18","author":[{"given":"Mathias","family":"Bendtsen","sequence":"first","affiliation":[{"name":"Institute of Biomedicine, Pharmacology, Aarhus University, Wilhelm Meyers All\u00e9 4, DK-8000 Aarhus C, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Grimm","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, Pharmacology, Aarhus University, Wilhelm Meyers All\u00e9 4, DK-8000 Aarhus C, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johann","family":"Bauer","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Wehland","sequence":"additional","affiliation":[{"name":"Clinic and Policlinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Wise","sequence":"additional","affiliation":[{"name":"Hematology\/Oncology, University of Southern California, Children\u2019s Hospital Los Angeles, 4650 Sunset Blvd. MS #57, Los Angeles, CA 90027, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nils","family":"Magnusson","sequence":"additional","affiliation":[{"name":"Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University, N\u00f8rrebrogade 44, DK-8000 Aarhus C, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manfred","family":"Infanger","sequence":"additional","affiliation":[{"name":"Clinic and Policlinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1120-0246","authenticated-orcid":false,"given":"Marcus","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Clinic and Policlinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"23024","DOI":"10.3390\/ijms151223024","article-title":"Anti-vascular endothelial growth factor therapy in breast cancer","volume":"15","author":"Kristensen","year":"2014","journal-title":"Int. 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