Megha Agarwal1, Nidhi Thareja2, Melody Benjamin3, Andre Akhondi4, George D Mitchell4. 1. Department of Cardiology, UCLA Health Ventura, 6633 Telephone Rd. Suite 212, Ventura, CA, 93003, USA. magarwal@mednet.ucla.edu. 2. Department of Cardiology, UCLA Health Santa Clarita, 25775 McBean Parkway Suite 202, Santa Clarita, CA, 91355, USA. 3. Department of Hematology/Oncology, UCLA Health Ventura, 6633 Telephone Rd. Suite 200, Ventura, CA, 93003, USA. 4. Department of Cardiology, UCLA Health Ventura, 6633 Telephone Rd. Suite 212, Ventura, CA, 93003, USA.
Abstract
PURPOSE OF REVIEW: The purpose of this paper is to identify commonly used tyrosine kinase inhibitors (TKIs) that are associated with hypertension, primarily, vascular endothelial growth factor (VEGF) signaling pathway (VSP) inhibitors. We review the incidence, mechanism, and strategies for management of TKI-induced HTN. We hope to provide clinicians with guidance on how to manage similar clinical scenarios. RECENT FINDINGS: Many of the newer VSP inhibitors are reviewed here, including cediranib, axitinib, pazopanib, and ponatinib. Trials utilizing prophylactic treatment with angiotensin system inhibitors (ASIs) are discussed as well as recent data showing an improvement in overall survival and progression-free survival in patients on ASIs and TKI-induced hypertension. The incidence of TKI-induced HTN among the VEGF inhibitors ranges from 5 to 80% and is dose dependent. Newer generation small-molecule TKIs has a lower incidence. The mechanism of action involves VSP inhibition, leading to decreased nitric oxide and increased endothelin production, which causes vasoconstriction, capillary rarefaction, and hypertension. ASIs and calcium channel blockers are first-line therapy for treatment and are associated with improved overall survival. Nitrates and beta-blockers are associated with in vitro cancer regression; however, there is a paucity of trials regarding their use as an anti-hypertensive agent in the TKI-induced HTN patient population.
PURPOSE OF REVIEW: The purpose of this paper is to identify commonly used tyrosine kinase inhibitors (TKIs) that are associated with hypertension, primarily, vascular endothelial growth factor (VEGF) signaling pathway (VSP) inhibitors. We review the incidence, mechanism, and strategies for management of TKI-induced HTN. We hope to provide clinicians with guidance on how to manage similar clinical scenarios. RECENT FINDINGS: Many of the newer VSP inhibitors are reviewed here, including cediranib, axitinib, pazopanib, and ponatinib. Trials utilizing prophylactic treatment with angiotensin system inhibitors (ASIs) are discussed as well as recent data showing an improvement in overall survival and progression-free survival in patients on ASIs and TKI-induced hypertension. The incidence of TKI-induced HTN among the VEGF inhibitors ranges from 5 to 80% and is dose dependent. Newer generation small-molecule TKIs has a lower incidence. The mechanism of action involves VSP inhibition, leading to decreased nitric oxide and increased endothelin production, which causes vasoconstriction, capillary rarefaction, and hypertension. ASIs and calcium channel blockers are first-line therapy for treatment and are associated with improved overall survival. Nitrates and beta-blockers are associated with in vitro cancer regression; however, there is a paucity of trials regarding their use as an anti-hypertensive agent in the TKI-induced HTN patient population.
Authors: Tejas V Patel; Jeffrey A Morgan; George D Demetri; Suzanne George; Robert G Maki; Michael Quigley; Benjamin D Humphreys Journal: J Natl Cancer Inst Date: 2008-02-12 Impact factor: 13.506
Authors: Paul K Whelton; Robert M Carey; Wilbert S Aronow; Donald E Casey; Karen J Collins; Cheryl Dennison Himmelfarb; Sondra M DePalma; Samuel Gidding; Kenneth A Jamerson; Daniel W Jones; Eric J MacLaughlin; Paul Muntner; Bruce Ovbiagele; Sidney C Smith; Crystal C Spencer; Randall S Stafford; Sandra J Taler; Randal J Thomas; Kim A Williams; Jeff D Williamson; Jackson T Wright Journal: Hypertension Date: 2017-11-13 Impact factor: 10.190
Authors: Moshe Talpaz; Neil P Shah; Hagop Kantarjian; Nicholas Donato; John Nicoll; Ron Paquette; Jorge Cortes; Susan O'Brien; Claude Nicaise; Eric Bleickardt; M Anne Blackwood-Chirchir; Vishwanath Iyer; Tai-Tsang Chen; Fei Huang; Arthur P Decillis; Charles L Sawyers Journal: N Engl J Med Date: 2006-06-15 Impact factor: 91.245
Authors: Emily S Robinson; Ursula A Matulonis; Percy Ivy; Suzanne T Berlin; Karin Tyburski; Richard T Penson; Benjamin D Humphreys Journal: Clin J Am Soc Nephrol Date: 2010-01-07 Impact factor: 8.237
Authors: Diana R Hernandez; Miguel G Rojas; Laisel Martinez; Boris L Rodriguez; Zachary M Zigmond; Roberto I Vazquez-Padron; Roberta M Lassance-Soares Journal: Biochem Biophys Res Commun Date: 2019-08-12 Impact factor: 3.575
Authors: Kaisa M Mäki-Petäjä; Adam McGeoch; Lucy L Yang; Annette Hubsch; Carmel M McEniery; Paul A R Meyer; Fraz Mir; Parag Gajendragadkar; Nicola Ramenatte; Gayathri Anandappa; Sara Santos Franco; Simon J Bond; Carola-Bibiane Schönlieb; Yoeri Boink; Christoph Brune; Ian B Wilkinson; Duncan I Jodrell; Joseph Cheriyan Journal: Hypertension Date: 2021-03-29 Impact factor: 10.190
Authors: Bo Hyun Kim; Su Jong Yu; Wonseok Kang; Sung Bum Cho; Soo Young Park; Seung Up Kim; Do Young Kim Journal: J Gastroenterol Hepatol Date: 2021-11-17 Impact factor: 4.369