Drug-Induced Hypertension Caused by Multikinase Inhibitors (Sorafenib, Sunitinib, Lenvatinib and Axitinib) in Renal Cell Carcinoma Treatment

Int J Mol Sci. 2019 Sep 23;20(19):4712. doi: 10.3390/ijms20194712.

Abstract

This paper reviews current treatments for renal cell carcinoma/cancer (RCC) with the multikinase inhibitors (MKIs) sorafenib, sunitinib, lenvatinib and axitinib. Furthermore, it compares these drugs regarding progression-free survival, overall survival and adverse effects (AE), with a focus on hypertension. Sorafenib and sunitinib, which are included in international clinical guidelines as first- and second-line therapy in metastatic RCC, are now being challenged by new-generation drugs like lenvatinib and axitinib. These drugs have shown significant clinical benefits for patients with RCC, but all four induce a variety of AEs. Hypertension is one of the most common AEs related to MKI treatment. Comparing sorafenib, sunitinib and lenvatinib revealed that sorafenib and sunitinib had the same efficacy, but sorafenib was safer to use. Lenvatinib showed better efficacy than sorafenib but worse safety. No trials have yet been completed that compare lenvatinib with sunitinib. Although axitinib promotes slightly higher hypertension rates compared to sunitinib, the overall discontinuation rate and cardiovascular complications are favourable. Although the mean rate of patients who develop hypertension is similar for each drug, some trials have shown large differences, which could indicate that lifestyle and/or genetic factors play an additional role.

Keywords: axitinib; hypertension; lenvatinib; multikinase inhibitor; renal cell carcinoma; sorafenib; sunitinib.

Publication types

  • Review

MeSH terms

  • Axitinib* / adverse effects
  • Axitinib* / therapeutic use
  • Carcinoma, Renal Cell* / drug therapy
  • Carcinoma, Renal Cell* / pathology
  • Carcinoma, Renal Cell* / physiopathology
  • Humans
  • Hypertension* / chemically induced
  • Hypertension* / physiopathology
  • Kidney Neoplasms* / drug therapy
  • Kidney Neoplasms* / pathology
  • Kidney Neoplasms* / physiopathology
  • Phenylurea Compounds* / adverse effects
  • Phenylurea Compounds* / therapeutic use
  • Quinolines* / adverse effects
  • Quinolines* / therapeutic use
  • Sorafenib* / adverse effects
  • Sorafenib* / therapeutic use
  • Sunitinib* / adverse effects
  • Sunitinib* / therapeutic use

Substances

  • Phenylurea Compounds
  • Quinolines
  • Sorafenib
  • Axitinib
  • lenvatinib
  • Sunitinib