title: Effects and Side Effects of Using Sorafenib and Sunitinib in the Treatment of Metastatic Renal Cell Carcinoma.
abstract: In recent years, targeted therapies have proven beneficial in terms of progression-free survival (PFS) and overall survival (OS) in the treatment of metastatic renal cell carcinoma (mRCC). The tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib are included in international clinical guidelines as first-line and second-line therapy in mRCC. Hypertension is an adverse effect of these drugs and the degree of hypertension associates with the anti-tumour effect. Studies have compared newer targeted drugs to sorafenib and sunitinib in terms of PFS, OS, quality of life and safety profiles. Phase III studies presented promising response rates and acceptable safety profiles of axitinib and tivozanib compared to sorafenib, and a phase II study reported greater efficacy using a combination of bevacizumab and IFN-α compared to sunitinib. Treatment with nintedanib exhibited a notably low prevalence of hypertension compared to sunitinib. The use of sorafenib and sunitinib are challenged by new drugs, but do not appear likely to be substituted in the near future. To clarify whether newer targeted drugs should replace sorafenib and sunitinib, more research is needed. This manuscript reviews the current utility and adverse effects of sorafenib and sunitinib and newer targeted therapies in the treatment of mRCC.
authors.affiliation: Institute of Biomedicine, Pharmacology, Aarhus University, Wilhelm Meyers Allé 4, DK-8000 Aarhus C, Denmark. carolinerandruph@gmail.com.
authors.forename: Caroline
authors.initials: C
authors.lastname: Randrup Hansen
authors.affiliation: Institute of Biomedicine, Pharmacology, Aarhus University, Wilhelm Meyers Allé 4, DK-8000 Aarhus C, Denmark. dgg@biomed.au.dk.
authors.forename: Daniela
authors.initials: D
authors.lastname: Grimm
authors.affiliation: Max Planck Institute for Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany. jbauer@biochem.mpg.de.
authors.forename: Johann
authors.initials: J
authors.lastname: Bauer
authors.affiliation: Clinic and Policlinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany. markus.wehland@med.ovgu.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Wehland
authors.affiliation: Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University, Nørrebrogade 44, DK-8000 Aarhus C, Denmark. nm@clin.au.dk.
authors.forename: Nils E
authors.initials: NE
authors.lastname: Magnusson
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology*; D019468:Disease Management; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D000077157:Sorafenib; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib
keywords: hypertension; metastatic renal cell carcinoma; sorafenib; sunitinib; tyrosine kinase inhibitors; vascular endothelial growth factor