Hypertension Caused by Lenvatinib and Everolimus in the Treatment of Metastatic Renal Cell Carcinoma.

Abstract

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.

• Authors: Mathias Alrø Fichtner Bendtsen, Daniela Grimm, Johann Bauer, Markus Wehland, Petra Wise, Nils E Magnusson, Manfred Infanger, Marcus Krüger
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 18 Issue 8 (Aug 10 2017) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 28796163 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents
• Phenylurea Compounds
• Protein Kinase Inhibitors
• Quinolines
• Everolimus
• MTOR protein, human
• TOR Serine-Threonine Kinases
• lenvatinib

Topics

• Animals
• Antineoplastic Agents (adverse effects, therapeutic use)
• Carcinoma, Renal Cell (drug therapy, pathology)
• Everolimus (adverse effects, therapeutic use)
• Humans
• Hypertension (chemically induced)
• Kidney Neoplasms (drug therapy, pathology)
• Neoplasm Metastasis (drug therapy, pathology)
• Phenylurea Compounds (adverse effects, therapeutic use)
• Protein Kinase Inhibitors (adverse effects, therapeutic use)
• Quinolines (adverse effects, therapeutic use)
• TOR Serine-Threonine Kinases (antagonists & inhibitors)