title: Tyrosine Kinase and Mammalian Target of Rapamycin Inhibitors in the Treatment of Advanced Renal Cell Carcinoma: Practical Clinical Implications of Pharmacologic Features.
abstract: The development of multiple vascular endothelial growth factor- and mammalian target of rapamycin-targeted therapies in advanced renal cell carcinoma has resulted in significant clinical benefit. However, the availability of multiple treatment options has led to a more complicated clinical decision-making process. Prognostic factors have been incorporated into the inclusion criteria for pivotal clinical trials and have thus provided some guidance regarding the selection and sequencing of therapy. Even within a given patient risk group and particular line of therapy, questions remain regarding the optimal choice of a targeted agent. The present review provides a practical, clinician-oriented assessment of pharmacologic factors that should be considered when a receptor tyrosine kinase or mammalian target of rapamycin kinase inhibitor is used to treat patients with advanced or metastatic renal cell carcinoma. Although these 2 classes of agents have different mechanisms of action, they are metabolized by similar pathways, resulting in broadly similar pharmacokinetic and drug-drug interaction profiles. To further individualize therapy and optimize clinical benefit, an enhanced understanding of the key pharmacologic features that differentiate these agents is important.
authors.affiliation: Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA.
authors.forename: Rahul A
authors.initials: RA
authors.lastname: Parikh
authors.affiliation: Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA. Electronic address: applemanlj@upmc.edu.
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Appleman
authors.affiliation: University of Pittsburgh School of Pharmacy, Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Beumer
authors.affiliation: Pfizer Oncology, New York, NY.
authors.forename: Ewa
authors.initials: E
authors.lastname: Matczak
authors.affiliation: Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA.
authors.forename: Edward
authors.initials: E
authors.lastname: Chu
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism; D000066491:Clinical Decision-Making; D002986:Clinical Trials as Topic; D004347:Drug Interactions; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D058570:TOR Serine-Threonine Kinases
keywords: Decision-making; Kidney cancer; Management; Pharmacology; Targeted therapy