Optimizing treatment of renal cell carcinoma with VEGFR-TKIs: a comparison of clinical pharmacology and drug-drug interactions of anti-angiogenic drugs

Stefano Fogli; Camillo Porta; Marzia Del Re; Stefania Crucitta; Giulia Gianfilippo; Romano Danesi; Brian I Rini; Manuela Schmidinger

doi:10.1016/j.ctrv.2020.101966

Optimizing treatment of renal cell carcinoma with VEGFR-TKIs: a comparison of clinical pharmacology and drug-drug interactions of anti-angiogenic drugs

Cancer Treat Rev. 2020 Mar:84:101966. doi: 10.1016/j.ctrv.2020.101966. Epub 2020 Jan 17.

Authors

Stefano Fogli¹, Camillo Porta², Marzia Del Re¹, Stefania Crucitta¹, Giulia Gianfilippo¹, Romano Danesi³, Brian I Rini⁴, Manuela Schmidinger⁵

Affiliations

¹ Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
² Department of Internal Medicine, University of Pavia and Division of Translational Oncology, IRCCS Istituti Clinici Scientifici Maugeri, Pavia, Italy.
³ Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. Electronic address: [email protected].
⁴ Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
⁵ Clinical Division of Oncology, Department of Medicine I and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

PMID: 32044644
DOI: 10.1016/j.ctrv.2020.101966

Abstract

Anti-angiogenic treatment is an important option that has changed the therapeutic landscape in various tumors, particularly in patients affected by renal cell carcinoma (RCC). Agents that block signaling pathways governing tumor angiogenesis have raised high expectations among clinicians. Vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) comprise a heterogeneous class of drugs with distinct pharmacological profiles, including potency, selectivity, pharmacokinetics and drug-drug interactions. Among them, tivozanib is one of the last TKIs introduced in the clinical practice; this drug selectively targets VEGFRs, it is characterized by a favorable pharmacokinetics and safety profile and has been approved as first-line treatment for patients with metastatic RCC (mRCC). In this article, we describe the clinical pharmacology of selected VEGFR-TKIs used for the treatment of mRCC, highlighting the relevant differences; moreover we aim to define the main pharmacologic characteristics of these drug.

Keywords: Angiogenesis; Pharmacology; RCC; Tivozanib; VEGFR-TKIs.

Publication types

Comparative Study
Review

MeSH terms

Angiogenesis Inhibitors / adverse effects
Angiogenesis Inhibitors / pharmacology*
Angiogenesis Inhibitors / therapeutic use
Anilides / adverse effects
Anilides / pharmacology
Anilides / therapeutic use
Axitinib / adverse effects
Axitinib / pharmacology
Axitinib / therapeutic use
Carcinoma, Renal Cell / drug therapy*
Drug Interactions
Humans
Indazoles
Kidney Neoplasms / drug therapy*
Phenylurea Compounds / adverse effects
Phenylurea Compounds / pharmacology
Phenylurea Compounds / therapeutic use
Protein Kinase Inhibitors / adverse effects
Protein Kinase Inhibitors / pharmacology*
Protein Kinase Inhibitors / therapeutic use
Pyridines / adverse effects
Pyridines / pharmacology
Pyridines / therapeutic use
Pyrimidines / adverse effects
Pyrimidines / pharmacology
Pyrimidines / therapeutic use
Quinolines / adverse effects
Quinolines / pharmacology
Quinolines / therapeutic use
Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
Sorafenib / adverse effects
Sorafenib / pharmacology
Sorafenib / therapeutic use
Sulfonamides / adverse effects
Sulfonamides / pharmacology
Sulfonamides / therapeutic use
Sunitinib / adverse effects
Sunitinib / pharmacology
Sunitinib / therapeutic use

Substances

Angiogenesis Inhibitors
Anilides
Indazoles
Phenylurea Compounds
Protein Kinase Inhibitors
Pyridines
Pyrimidines
Quinolines
Sulfonamides
tivozanib
cabozantinib
pazopanib
Sorafenib
Axitinib
Receptors, Vascular Endothelial Growth Factor
lenvatinib
Sunitinib