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

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.

Cancer treatment reviews. 2020 Jan 17 [Epub ahead of print]

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

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