PMID- 28796163
OWN - NLM
STAT- MEDLINE
DCOM- 20180501
LR  - 20211204
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 18
IP  - 8
DP  - 2017 Aug 10
TI  - Hypertension Caused by Lenvatinib and Everolimus in the Treatment of Metastatic 
      Renal Cell Carcinoma.
LID - 10.3390/ijms18081736 [doi]
LID - 1736
AB  - 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.
FAU - Bendtsen, Mathias Alro Fichtner
AU  - Bendtsen MAF
AD  - Institute of Biomedicine, Pharmacology, Aarhus University, Wilhelm Meyers Alle 4, 
      DK-8000 Aarhus C, Denmark. bendtsen_mat@hotmail.com.
FAU - Grimm, Daniela
AU  - Grimm D
AD  - Institute of Biomedicine, Pharmacology, Aarhus University, Wilhelm Meyers Alle 4, 
      DK-8000 Aarhus C, Denmark. dgg@biomed.au.dk.
FAU - Bauer, Johann
AU  - Bauer J
AD  - Max Planck Institute for Biochemistry, Am Klopferspitz 18, 82152 Martinsried, 
      Germany. jbauer@biochem.mpg.de.
FAU - Wehland, Markus
AU  - Wehland M
AD  - Clinic and Policlinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke 
      University, Leipziger Str. 44, 39120 Magdeburg, Germany. 
      markus.wehland@med.ovgu.de.
FAU - Wise, Petra
AU  - Wise P
AD  - Hematology/Oncology, University of Southern California, Children's Hospital Los 
      Angeles, 4650 Sunset Blvd. MS #57, Los Angeles, CA 90027, USA. 
      pwise@chla.usc.edu.
FAU - Magnusson, Nils E
AU  - Magnusson NE
AD  - Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, 
      Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark. nm@clin.au.dk.
FAU - Infanger, Manfred
AU  - Infanger M
AD  - Clinic and Policlinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke 
      University, Leipziger Str. 44, 39120 Magdeburg, Germany. 
      manfred.infanger@med.ovgu.de.
FAU - Kruger, Marcus
AU  - Kruger M
AD  - Clinic and Policlinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke 
      University, Leipziger Str. 44, 39120 Magdeburg, Germany. 
      marcus.krueger@med.ovgu.de.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20170810
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinolines)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EE083865G2 (lenvatinib)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*adverse effects/therapeutic use
MH  - Carcinoma, Renal Cell/*drug therapy/pathology
MH  - Everolimus/*adverse effects/therapeutic use
MH  - Humans
MH  - Hypertension/*chemically induced
MH  - Kidney Neoplasms/*drug therapy/pathology
MH  - Neoplasm Metastasis/drug therapy/pathology
MH  - Phenylurea Compounds/*adverse effects/therapeutic use
MH  - Protein Kinase Inhibitors/*adverse effects/therapeutic use
MH  - Quinolines/*adverse effects/therapeutic use
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors
PMC - PMC5578126
OTO - NOTNLM
OT  - everolimus
OT  - hypertension
OT  - lenvatinib
OT  - mTOR inhibitor
OT  - metastatic renal cell carcinoma
OT  - multikinase inhibitors
OT  - vascular endothelial growth factor
COIS- The authors declare no conflict of interest.
EDAT- 2017/08/11 06:00
MHDA- 2018/05/02 06:00
PMCR- 2017/08/01
CRDT- 2017/08/11 06:00
PHST- 2017/07/13 00:00 [received]
PHST- 2017/08/04 00:00 [revised]
PHST- 2017/08/08 00:00 [accepted]
PHST- 2017/08/11 06:00 [entrez]
PHST- 2017/08/11 06:00 [pubmed]
PHST- 2018/05/02 06:00 [medline]
PHST- 2017/08/01 00:00 [pmc-release]
AID - ijms18081736 [pii]
AID - ijms-18-01736 [pii]
AID - 10.3390/ijms18081736 [doi]
PST - epublish
SO  - Int J Mol Sci. 2017 Aug 10;18(8):1736. doi: 10.3390/ijms18081736.