Anlotinib-Induced Hypertension: Current Concepts and Future Prospects

Bing       Lv; Jing       Chen; Xiao-Liang       Liu
doi:10.2174/1381612827666211006145141
Abstract

Background: Anlotinib is a new tyrosine kinase inhibitor developed in China that targets the receptors for vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factor, and stem cell factor. Therefore, anlotinib inhibits tumor angiogenesis, representing a new therapeutic alternative for lung cancer. Hypertension is one of its most common adverse effects, leading to discontinuation of the drug and limited clinical usefulness.
Objective: The present review aims to summarize the evidence on the prevalence, physiopathology, and management of anlotinib-induced hypertension, as well as its effect on the cancer prognosis.
Methods: Searches in Medline, Cochrane Central Library, and Embase were performed using the following terms: anlotinib, adverse effect, hypertension, clinical trial, vascular endothelial growth factor, and anti-angiogenic drugs. Citations were also identified by checking the reference sections of selected papers.
Results: Except for a phase I clinical trial with a small sample size (n = 6), almost all the clinical trials on anlotinib have reported the development of anlotinib-induced hypertension. In these trials, the incidence of hypertension ranged from 13% to 67.7%, and that of grade 3/4 hypertension ranged from 4.8% to 16%. Alterations in nitric oxide, endothelin-1, microvascular rarefaction, selective vasoconstrictions, and renal injury have been cited as potential mechanisms leading to anlotinib-induced hypertension. When needed, treatment may include general hygienic measures and pharmacotherapy in some cases.
Conclusion: To effectively manage anlotinib-induced hypertension, early prevention, a reasonable dosage regimen, and appropriate treatment are critical to effectively manage anlotinib-induced hypertension. Additionally, anlotinib-induced hypertension may be considered a marker for predicting efficacy.
Keywords: Anlotinib, adverse effect, hypertension, clinical trial, vascular endothelial growth factor, anti-angiogenic drugs, tyrosine kinase inhibitor.
« Previous Next »
[1] 
Bruix J, Qin S, Merle P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet  2017; 389(10064): 56-66.
[http://dx.doi.org/10.1016/S0140-6736(16)32453-9] [PMID: 27932229] 
[2] 
Tomasello G, Petrelli F, Ghidini M, Russo A, Passalacqua R, Barni S. FOLFOXIRI plus bevacizumab as conversion therapy for patients with initially unresectable metastatic colorectal cancer: A systematic review and pooled analysis. JAMA Oncol  2017; 3(7): e170278.
[http://dx.doi.org/10.1001/jamaoncol.2017.0278] [PMID: 28542671] 
[3] 
Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med  2006; 355(24): 2542-50.
[http://dx.doi.org/10.1056/NEJMoa061884] [PMID: 17167137] 
[4] 
Xie C, Wan X, Quan H, et al. Preclinical characterization of anlotinib, a highly potent and selective vascular endothelial growth factor receptor-2 inhibitor. Cancer Sci  2018; 109(4): 1207-19.
[http://dx.doi.org/10.1111/cas.13536] [PMID: 29446853] 
[5] 
Shen G, Zheng F, Ren D, et al. Anlotinib: A novel multi-targeting tyrosine kinase inhibitor in clinical development. J Hematol Oncol  2018; 11(1): 120.
[http://dx.doi.org/10.1186/s13045-018-0664-7] [PMID: 30231931] 
[6] 
Syed YY. Anlotinib: First global approval. Drugs  2018; 78(10): 1057-62.
[http://dx.doi.org/10.1007/s40265-018-0939-x] [PMID: 29943374] 
[7] 
Song F, Hu B, Cheng JW, et al. Anlotinib suppresses tumor progressionviablocking the VEGFR2/PI3K/AKT cascade in intrahepatic cholangiocarcinoma. Cell Death Dis  2020; 11(7): 573.
[http://dx.doi.org/10.1038/s41419-020-02749-7] [PMID: 32709873] 
[8] 
Ma Z, Lu S, Zhou H, Zhang S, Wang Y, Lin N. Determination of intracellular anlotinib, osimertinib, afatinib and gefitinib accumulations in human brain microvascular endothelial cells by liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom  2021; 35(1): e8955.
[http://dx.doi.org/10.1002/rcm.8955] [PMID: 32990383] 
[9] 
Si X, Zhang L, Wang H, et al. Management of anlotinib-related adverse events in patients with advanced non-small cell lung cancer: Experiences in ALTER-0303. Thorac Cancer  2019; 10(3): 551-6.
[http://dx.doi.org/10.1111/1759-7714.12977] [PMID: 30666799] 
[10] 
Si X, Zhang L, Wang H, et al. Quality of life results from a randomized, double-blinded, placebo-controlled, multi-center phase III trial of anlotinib in patients with advanced non-small cell lung cancer. Lung Cancer  2018; 122: 32-7.
[http://dx.doi.org/10.1016/j.lungcan.2018.05.013] [PMID: 30032842] 
[11] 
Gao Y, Liu P, Shi R. Anlotinib as a molecular targeted therapy for tumors. Oncol Lett  2020; 20(2): 1001-14.
[http://dx.doi.org/10.3892/ol.2020.11685] [PMID: 32724339] 
[12] 
Lin B, Song X, Yang D, Bai D, Yao Y, Lu N. Anlotinib inhibits angiogenesisviasuppressing the activation of VEGFR2, PDGFRβ and FGFR1. Gene  2018; 654: 77-86.
[http://dx.doi.org/10.1016/j.gene.2018.02.026] [PMID: 29454091] 
[13] 
Zhou AP, Bai Y, Song Y, et al. Anlotinib versus sunitinib as first- line treatment for metastatic renal cell carcinoma: a randomized phase II clinical trial. Oncologist  2019; 24(8): e702-8.
[http://dx.doi.org/10.1634/theoncologist.2018-0839] [PMID: 30902918] 
[14] 
Zhong Y, Wei Q, Lu Y, Tang X, Wang Z, Chen L. Efficacy and safety of anlotinib in patients with advanced non-small cell lung cancer. J Thorac Dis  2020; 12(10): 6016-22.
[http://dx.doi.org/10.21037/jtd-20-2855] [PMID: 33209434] 
[15] 
Qiang H, Chang Q, Xu J, et al. New advances in antiangiogenic combination therapeutic strategies for advanced non-small cell lung cancer. J Cancer Res Clin Oncol  2020; 146(3): 631-45.
[http://dx.doi.org/10.1007/s00432-020-03129-6] [PMID: 32065262] 
[16] 
Zhou M, Chen X, Zhang H, et al. China national medical products administration approval summary: Anlotinib for the treatment of advanced non-small cell lung cancer after two lines of chemotherapy. Cancer Commun (Lond)  2019; 39(1): 36.
[http://dx.doi.org/10.1186/s40880-019-0383-7] [PMID: 31221221] 
[17] 
Zhao D, Xie B, Yang Y, Yan P, Liang SN, Lin Q. Progress in immunotherapy for small cell lung cancer. World J Clin Oncol  2020; 11(6): 370-7.
[http://dx.doi.org/10.5306/wjco.v11.i6.370] [PMID: 32874950] 
[18] 
Wang J, Wu DX, Meng L, Ji G. Anlotinib combined with SOX regimen (S1 (tegafur, gimeracil and oteracil porassium capsules) + oxaliplatin) in treating stage IV gastric cancer: study protocol for a single-armed and single-centred clinical trial. BMJ Open  2020; 10(6): e034685.
[http://dx.doi.org/10.1136/bmjopen-2019-034685] [PMID: 32499264] 
[19] 
Sun L, Yang M, Zhang X, et al. Anlotinib combined with etoposide for platinum-resistant recurrent ovarian cancer: A case report. Medicine (Baltimore)  2020; 99(20): e20053.
[http://dx.doi.org/10.1097/MD.0000000000020053] [PMID: 32443311] 
[20] 
Guo W, Chen S, Wu Z, Zhuang W, Yang J. Efficacy and safety of transarterial chemoembolization combined with anlotinib for unresectable hepatocellular carcinoma: A retrospective study. Technol Cancer Res Treat  2020; 19: 1533033820965587.
[http://dx.doi.org/10.1177/1533033820965587] [PMID: 33089769] 
[21] 
Ruan X, Shi X, Dong Q, et al. Antitumor effects of anlotinib in thyroid cancer. Endocr Relat Cancer  2019; 26(1): 153-64.
[http://dx.doi.org/10.1530/ERC-17-0558] [PMID: 30139768] 
[22] 
Wu D, Nie J, Dai L, et al. Salvage treatment with anlotinib for advanced non-small cell lung cancer. Thorac Cancer  2019; 10(7): 1590-6.
[http://dx.doi.org/10.1111/1759-7714.13120] [PMID: 31183998] 
[23] 
Zhang K, Ma X, Gao H, et al. Efficacy and safety of anlotinib in advanced non-small cell lung cancer: A real-world study. Cancer Manag Res  2020; 12: 3409-17.
[http://dx.doi.org/10.2147/CMAR.S246000] [PMID: 32494205] 
[24] 
Cheng Y, Du FC, Fang FQ, Duan ZJ, Lei W, Shi KG. Third-line treatment for metastatic colorectal cancer: Anlotinib is superior to chemotherapy and similar to fruquintinib or regorafenib. Neoplasma  2020; 67(6): 1384-90.
[http://dx.doi.org/10.4149/neo_2020_191125N1212] [PMID: 32657613] 
[25] 
Han B, Li K, Zhao Y, et al. Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer: A multicentre, randomised phase II trial (ALTER0302). Br J Cancer  2018; 118(5): 654-61.
[http://dx.doi.org/10.1038/bjc.2017.478] [PMID: 29438373] 
[26] 
Sun Y, Niu W, Du F, et al. Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors. J Hematol Oncol  2016; 9(1): 105.
[http://dx.doi.org/10.1186/s13045-016-0332-8] [PMID: 27716285] 
[27] 
Liu Z, Yao W, Zhao Y, Liu O, Zhang P, Ge H. Efficacy and safety of anlotinib combined with liposomal doxorubicin followed by anlotinib maintenance in metastatic soft tissue sarcomas. Cancer Manag Res  2021; 13: 1009-16.
[http://dx.doi.org/10.2147/CMAR.S286322] [PMID: 33574700] 
[28] 
Zhai C, Zhang X, Ren L, et al. The efficacy and safety of anlotinib combined with pd-1 antibody for third-line or further-line treatment of patients with advanced non-small-cell lung cancer. Front Oncol  2021; 10: 619010.
[http://dx.doi.org/10.3389/fonc.2020.619010] [PMID: 33680942] 
[29] 
Han B, Li K, Wang Q, et al. Effect of anlotinib as a third-line or further treatment on overall survival of patients with advanced non-small cell lung cancer: The alter 0303 phase 3 randomized clinical trial. JAMA Oncol  2018; 4(11): 1569-75.
[http://dx.doi.org/10.1001/jamaoncol.2018.3039] [PMID: 30098152] 
[30] 
Chu C, Shang W, Sun Y, Zhang X. Anlotinib is effective in patients with advanced oral cancer? Med Hypotheses  2020; 137: 109578.
[http://dx.doi.org/10.1016/j.mehy.2020.109578] [PMID: 32001416] 
[31] 
Wang L, He Z, Yang S, et al. The impact of previous therapy strategy on the efficiency of anlotinib hydrochloride as a third-line treatment on patients with advanced non-small cell lung cancer (NSCLC): A subgroup analysis of ALTER0303 trial. Transl Lung Cancer Res  2019; 8(5): 575-83.
[http://dx.doi.org/10.21037/tlcr.2019.09.21] [PMID: 31737494] 
[32] 
Zhong RB, Xu JL, Lou YQ, Chu TQ, Zhong H, Han BH. Anlotinib or platinum-pemetrexed as second-line therapy in EGFR T790M-negative lung cancer. Ann Palliat Med  2020; 9(4): 1681-7.
[http://dx.doi.org/10.21037/apm-20-105] [PMID: 32575999] 
[33] 
Zhang X, Peng L, Xie Q, Wu Q, Sheng X. Hypertensive retinopathy secondary to anlotinib treatment. Front Pharmacol  2020; 11: 843.
[http://dx.doi.org/10.3389/fphar.2020.00843] [PMID: 32581802] 
[34] 
Jiang B, Li J, Chen J, Xiang X, Xiong J, Deng J. Aortic dissection in a patient treated with anlotinib for metastatic lung squamous cell carcinoma. Thorac Cancer  2020; 11(2): 461-4.
[http://dx.doi.org/10.1111/1759-7714.13288] [PMID: 31891239] 
[35] 
Liu Y, Liu L, Liu L, et al. A phase I study investigation of metabolism, and disposition of [14C]-anlotinib after an oral administration in patients with advanced refractory solid tumors. Cancer Chemother Pharmacol  2020; 85(5): 907-15.
[http://dx.doi.org/10.1007/s00280-020-04062-8] [PMID: 32266457] 
[36] 
Chi Y, Fang Z, Hong X, et al. Safety and efficacy of anlotinib, a multikinase angiogenesis inhibitor, in patients with refractory metastatic soft-tissue sarcoma. Clin Cancer Res  2018; 24(21): 5233-8.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-3766] [PMID: 29895706] 
[37] 
Sun Y, Du F, Gao M, et al. Anlotinib for the treatment of patients with locally advanced or metastatic medullary Thyroid Cancer. Thyroid  2018; 28(11): 1455-61.
[http://dx.doi.org/10.1089/thy.2018.0022] [PMID: 30142994] 
[38] 
Wu D, Nie J, Hu W, et al. A phase II study of anlotinib in 45 patients with relapsed small cell lung cancer. Int J Cancer  2020; 147(12): 3453-60.
[http://dx.doi.org/10.1002/ijc.33161] [PMID: 32557583] 
[39] 
Huang J, Xiao J, Fang W, et al. Anlotinib for previously treated advanced or metastatic esophageal squamous cell carcinoma: A double-blind randomized phase 2 trial. Cancer Med  2021; 10(5): 1681-9.
[http://dx.doi.org/10.1002/cam4.3771] [PMID: 33586360] 
[40] 
Ma J, Song Y, Shou J, et al. Anlotinib for patients with metastatic renal cell carcinoma previously treated with one vascular endothelial growth factor receptor-tyrosine kinase inhibitor: A phase 2 trial. Front Oncol  2020; 10: 664.
[http://dx.doi.org/10.3389/fonc.2020.00664] [PMID: 32457838] 
[41] 
Carter JJ, Fretwell LV, Woolard J. Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats. FASEB J  2017; 31(3): 1193-203.
[http://dx.doi.org/10.1096/fj.201600749R] [PMID: 27986807] 
[42] 
Agarwal M, Thareja N, Benjamin M, Akhondi A, Mitchell GD. Tyrosine kinase inhibitor-induced hypertension. Curr Oncol Rep  2018; 20(8): 65.
[http://dx.doi.org/10.1007/s11912-018-0708-8] [PMID: 29931399] 
[43] 
Dobbin SJH, Cameron AC, Petrie MC, Jones RJ, Touyz RM, Lang NN. Toxicity of cancer therapy: What the cardiologist needs to know about angiogenesis inhibitors. Heart  2018; 104(24): 1995-2002.
[http://dx.doi.org/10.1136/heartjnl-2018-313726] [PMID: 30228246] 
[44] 
Gadd M, Pranavan G, Malik L. Association between tyrosine-kinase inhibitor induced hypertension and treatment outcomes in metastatic renal cancer. Cancer Rep (Hoboken)  2020; 3(5): e1275.
[http://dx.doi.org/10.1002/cnr2.1275] [PMID: 32767664] 
[45] 
Thijs AM, van Herpen CM, Sweep FC, et al. Role of endogenous vascular endothelial growth factor in endothelium-dependent vasodilation in humans. Hypertension  2013; 61(5): 1060-5.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.00841] [PMID: 23509076] 
[46] 
Nakagawa T. Uncoupling of the VEGF-endothelial nitric oxide axis in diabetic nephropathy: An explanation for the paradoxical effects of VEGF in renal disease. Am J Physiol Renal Physiol  2007; 292(6): F1665-72.
[http://dx.doi.org/10.1152/ajprenal.00495.2006] [PMID: 17545302] 
[47] 
Wang H, Qiu L, Ma Y, et al. Naoxintong inhibits myocardial infarction injury by VEGF/eNOS signaling-mediated neovascularization. J Ethnopharmacol  2017; 209: 13-23.
[http://dx.doi.org/10.1016/j.jep.2017.06.040] [PMID: 28669772] 
[48] 
Sane DC, Anton L, Brosnihan KB. Angiogenic growth factors and hypertension. Angiogenesis  2004; 7(3): 193-201.
[http://dx.doi.org/10.1007/s10456-004-2699-3] [PMID: 15609074] 
[49] 
Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med  2003; 9(6): 669-76.
[http://dx.doi.org/10.1038/nm0603-669] [PMID: 12778165] 
[50] 
Li B, Ogasawara AK, Yang R, et al. KDR (VEGF receptor 2) is the major mediator for the hypotensive effect of VEGF. Hypertension  2002; 39(6): 1095-100.
[http://dx.doi.org/10.1161/01.HYP.0000018588.56950.7A] [PMID: 12052848] 
[51] 
Henry TD, Annex BH, McKendall GR, et al. The VIVA trial: Vascular endothelial growth factor in ischemia for vascular angiogenesis. Circulation  2003; 107(10): 1359-65.
[http://dx.doi.org/10.1161/01.CIR.0000061911.47710.8A] [PMID: 12642354] 
[52] 
Kappers MH, van Esch JH, Sleijfer S, Danser AH, van den Meiracker AH. Cardiovascular and renal toxicity during angiogenesis inhibition: Clinical and mechanistic aspects. J Hypertens  2009; 27(12): 2297-309.
[http://dx.doi.org/10.1097/HJH.0b013e3283309b59] [PMID: 19680138] 
[53] 
Zou AP, Cowley AW Jr. Role of nitric oxide in the control of renal function and salt sensitivity. Curr Hypertens Rep  1999; 1(2): 178-86.
[http://dx.doi.org/10.1007/s11906-999-0016-7] [PMID: 10981063] 
[54] 
Mourad JJ, des Guetz G, Debbabi H, Levy BI. Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation. Ann Oncol  2008; 19(5): 927-34.
[http://dx.doi.org/10.1093/annonc/mdm550] [PMID: 18056916] 
[55] 
Corti F, Simons M. Modulation of VEGF receptor 2 signaling by protein phosphatases. Pharmacol Res  2017; 115: 107-23.
[http://dx.doi.org/10.1016/j.phrs.2016.11.022] [PMID: 27888154] 
[56] 
Amraoui F, Spijkers L, Hassani Lahsinoui H, et al. SFlt-1 elevates blood pressure by augmenting endothelin-1-mediated vasoconstriction in mice. PLoS One  2014; 9(3): e91897.
[http://dx.doi.org/10.1371/journal.pone.0091897] [PMID: 24632840] 
[57] 
Lygnos MC, Pappa KI, Papadaki HA, et al. Changes in maternal plasma levels of VEGF, bFGF, TGF-beta1, ET-1 and sKL during uncomplicated pregnancy, hypertensive pregnancy and gestational diabetes.  in vivo 2006; 20(1): 157-63.
[PMID: 16433046] 
[58] 
Houde M, Desbiens L, D’Orléans-Juste P. Endothelin-1: Biosynthesis, signaling and vasoreactivity. Adv Pharmacol  2016; 77: 143-75.
[http://dx.doi.org/10.1016/bs.apha.2016.05.002] [PMID: 27451097] 
[59] 
Stauffer BL, Westby CM, DeSouza CA. Endothelin-1, aging and hypertension. Curr Opin Cardiol  2008; 23(4): 350-5.
[http://dx.doi.org/10.1097/HCO.0b013e328302f3c6] [PMID: 18520719] 
[60] 
Czopek A, Moorhouse R, Guyonnet L, et al. A novel role for myeloid endothelin-B receptors in hypertension. Eur Heart J  2019; 40(9): 768-84.
[http://dx.doi.org/10.1093/eurheartj/ehy881] [PMID: 30657897] 
[61] 
Lankhorst S, Baelde HJ, Kappers MH, et al. Greater sensitivity of blood pressure than renal toxicity to tyrosine kinase receptor inhibition with sunitinib. Hypertension  2015; 66(3): 543-9.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.115.05435] [PMID: 26195484] 
[62] 
Kappers MH, van Esch JH, Sluiter W, Sleijfer S, Danser AH, van den Meiracker AH. Hypertension induced by the tyrosine kinase inhibitor sunitinib is associated with increased circulating endothelin-1 levels. Hypertension  2010; 56(4): 675-81.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.149690] [PMID: 20733093] 
[63] 
Saleh L, Verdonk K, Visser W, van den Meiracker AH, Danser AH. The emerging role of endothelin-1 in the pathogenesis of pre-eclampsia. Ther Adv Cardiovasc Dis  2016; 10(5): 282-93.
[http://dx.doi.org/10.1177/1753944715624853] [PMID: 26755746] 
[64] 
Lankhorst S, Kappers MH, van Esch JH, Danser AH, van den Meiracker AH. Mechanism of hypertension and proteinuria during angiogenesis inhibition: Evolving role of endothelin-1. J Hypertens  2013; 31(3): 444-54.
[http://dx.doi.org/10.1097/HJH.0b013e32835c1d1b] [PMID: 23221987] 
[65] 
Lankhorst S, Kappers MH, van Esch JH, Danser AH, van den Meiracker AH. Hypertension during vascular endothelial growth factor inhibition: Focus on nitric oxide, endothelin-1, and oxidative stress. Antioxid Redox Signal  2014; 20(1): 135-45.
[http://dx.doi.org/10.1089/ars.2013.5244] [PMID: 23458507] 
[66] 
Elmarakby AA, Loomis ED, Pollock JS, Pollock DM. NADPH oxidase inhibition attenuates oxidative stress but not hypertension produced by chronic ET-1. Hypertension  2005; 45(2): 283-7.
[http://dx.doi.org/10.1161/01.HYP.0000153051.56460.6a] [PMID: 15623539] 
[67] 
Feihl F, Liaudet L, Waeber B, Levy BI. Hypertension: A disease of the microcirculation? Hypertension  2006; 48(6): 1012-7.
[http://dx.doi.org/10.1161/01.HYP.0000249510.20326.72] [PMID: 17060505] 
[68] 
Touyz RM, Lang NN, Herrmann J, van den Meiracker AH, Danser AHJ. Recent advances in hypertension and cardiovascular toxicities with vascular endothelial growth factor inhibition. Hypertension  2017; 70(2): 220-6.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.08856] [PMID: 28630211] 
[69] 
Caletti S, Paini A, Coschignano MA, et al. Management of VEGF-targeted therapy-induced hypertension. Curr Hypertens Rep  2018; 20(8): 68.
[http://dx.doi.org/10.1007/s11906-018-0871-1] [PMID: 29959593] 
[70] 
Lin SL, Chang FC, Schrimpf C, et al. Targeting endothelium-pericyte cross talk by inhibiting VEGF receptor signaling attenuates kidney microvascular rarefaction and fibrosis. Am J Pathol  2011; 178(2): 911-23.
[http://dx.doi.org/10.1016/j.ajpath.2010.10.012] [PMID: 21281822] 
[71] 
Steeghs N, Rabelink TJ, op ’t Roodt J, et al. Reversibility of capillary density after discontinuation of bevacizumab treatment. Ann Oncol  2010; 21(5): 1100-5.
[http://dx.doi.org/10.1093/annonc/mdp417] [PMID: 19854721] 
[72] 
Boursiquot BC, Zabor EC, Glezerman IG, Jaimes EA. Hypertension and VEGF (Vascular Endothelial Growth Factor) receptor tyrosine kinase inhibition: Effects on renal function. Hypertension  2017; HYPERTENSIONAHA.117.09275.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.09275] [PMID: 28739979] 
[73] 
Kitamoto Y, Tokunaga H, Miyamoto K, Tomita K. VEGF is an essential molecule for glomerular structuring. Nephrol Dial Transplant  2002; 17(Suppl. 9): 25-7.
[http://dx.doi.org/10.1093/ndt/17.suppl_9.25] [PMID: 12386279] 
[74] 
Kanellis J, Paizis K, Cox AJ, et al. Renal ischemia-reperfusion increases endothelial VEGFR-2 without increasing VEGF or VEGFR-1 expression. Kidney Int  2002; 61(5): 1696-706.
[http://dx.doi.org/10.1046/j.1523-1755.2002.00329.x] [PMID: 11967019] 
[75] 
Maitland ML, Bakris GL, Black HR, et al. Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. J Natl Cancer Inst  2010; 102(9): 596-604.
[http://dx.doi.org/10.1093/jnci/djq091] [PMID: 20351338] 
[76] 
Liu L, Wang X, Wu WB, Zhang M. Salvage anlotinib showed sustained efficacy in heavily pretreated EGFR wild-type lung adenocarcinoma: A case report and review of the literature. Medicine (Baltimore)  2020; 99(41): e22707.
[http://dx.doi.org/10.1097/MD.0000000000022707] [PMID: 33031343] 
[77] 
Si XY, Wang HP, Zhang XT, Wang MZ, Zhang L. [Efficacy and safety of anlotinib in 16 patients with advanced non-small cell lung cancer]. Zhonghua Nei Ke Za Zhi  2018; 57(11): 830-4.
[PMID: 30392239] 
[78] 
[Chinese expert consensus on Anlotinib Hydrochloride for advanced lung cancer (2020 edition)]. Zhonghua Zhong Liu Za Zhi  2020; 42(10): 807-16.
[PMID: 33113621] 
[79] 
Liu LS. [2010 Chinese guidelines for the management of hypertension]. Zhonghua Xin Xue Guan Bing Za Zhi  2011; 39(7): 579-615.
[PMID: 22088239] 
[80] 
Robinson ES, Khankin EV, Karumanchi SA, Humphreys BD. Hypertension induced by vascular endothelial growth factor signaling pathway inhibition: Mechanisms and potential use as a biomarker. Semin Nephrol  2010; 30(6): 591-601.
[http://dx.doi.org/10.1016/j.semnephrol.2010.09.007] [PMID: 21146124] 
[81] 
Chung R, Tyebally S, Chen D, et al. Hypertensive cardiotoxicity in cancer treatment-systematic analysis of adjunct, conventional chemotherapy, and novel therapies-epidemiology, incidence, and pathophysiology. J Clin Med  2020; 9(10): 9.
[http://dx.doi.org/10.3390/jcm9103346] [PMID: 33081013] 
[82] 
Sun W, Wang Z, Chen R, et al. Influences of anlotinib on cytochrome P450 enzymes in rats using a cocktail method. BioMed Res Int  2017; 2017: 3619723.
[http://dx.doi.org/10.1155/2017/3619723] [PMID: 29441353] 
[83] 
Katsi V, Zerdes I, Manolakou S, et al. Anti-VEGF anticancer drugs: Mind the hypertension. Recent Adv Cardiovasc Drug Discov  2014; 9(2): 63-72.
[http://dx.doi.org/10.2174/1574890110999150604114127] [PMID: 26123049] 
[84] 
Faruque LI, Lin M, Battistella M, et al. Systematic review of the risk of adverse outcomes associated with vascular endothelial growth factor inhibitors for the treatment of cancer. PLoS One  2014; 9(7): e101145.
[http://dx.doi.org/10.1371/journal.pone.0101145] [PMID: 24988441] 
[85] 
Evans T. Utility of hypertension as a surrogate marker for efficacy of antiangiogenic therapy in NSCLC. Anticancer Res  2012; 32(11): 4629-38.
[PMID: 23155225] 
[86] 
Ravaud A, Sire M. Arterial hypertension and clinical benefit of sunitinib, sorafenib and bevacizumab in first and second-line treatment of metastatic renal cell cancer. Ann Oncol  2009; 20(5): 966-7.
[http://dx.doi.org/10.1093/annonc/mdp201] [PMID: 19403939] 
[87] 
Song PF, Xu N, Li Q. Efficacy and safety of anlotinib for elderly patients with previously treated extensive-stage sclc and the prognostic significance of common adverse reactions. Cancer Manag Res  2020; 12: 11133-43.
[http://dx.doi.org/10.2147/CMAR.S275624] [PMID: 33173346] 
[88] 
Cheng JD, Chai LX, Zhao ZP, Hao YY, Li S. Efficacy and safety of anlotinib for patients with advanced nsclc who progressed after standard regimens and the preliminary analysis of an efficacy predictor. Cancer Manag Res  2020; 12: 5641-50.
[http://dx.doi.org/10.2147/CMAR.S253366] [PMID: 32765067] 
[89] 
Horsley L, Marti K, Jayson GC. Is the toxicity of anti-angiogenic drugs predictive of outcome? A review of hypertension and proteinuria as biomarkers of response to anti-angiogenic therapy. Expert Opin Drug Metab Toxicol  2012; 8(3): 283-93.
[http://dx.doi.org/10.1517/17425255.2012.656845] [PMID: 22283844] 
[90] 
Budolfsen C, Faber J, Grimm D, et al. Tyrosine kinase inhibitor-induced hypertension: Role of hypertension as a biomarker in cancer treatment. Curr Vasc Pharmacol  2019; 17(6): 618-34.
[http://dx.doi.org/10.2174/1570161117666190130165810] [PMID: 30706818] 
[91] 
Österlund P, Soveri LM, Isoniemi H, Poussa T, Alanko T, Bono P. Hypertension and overall survival in metastatic colorectal cancer patients treated with bevacizumab-containing chemotherapy. Br J Cancer  2011; 104(4): 599-604.
[http://dx.doi.org/10.1038/bjc.2011.2] [PMID: 21304526] 
[92] 
Chen DS, Hurwitz H. Combinations of bevacizumab with cancer immunotherapy. Cancer J  2018; 24(4): 193-204.
[http://dx.doi.org/10.1097/PPO.0000000000000327] [PMID: 30119083] 
[93] 
Garber K. Promising early results for immunotherapy-antiangiogenesis combination. J Natl Cancer Inst  2014; 106(11): 106.
[http://dx.doi.org/10.1093/jnci/dju392] [PMID: 25421345] 
[94] 
Fukumura D, Kloepper J, Amoozgar Z, Duda DG, Jain RK. Enhancing cancer immunotherapy using antiangiogenics: Opportunities and challenges. Nat Rev Clin Oncol  2018; 15(5): 325-40.
[http://dx.doi.org/10.1038/nrclinonc.2018.29] [PMID: 29508855] 
[95] 
Furukawa K, Nagano T, Tachihara M, Yamamoto M, Nishimura Y. Interaction between immunotherapy and antiangiogenic therapy for cancer. Molecules  2020; 25(17): 25.
[http://dx.doi.org/10.3390/molecules25173900] [PMID: 32859106] 
[96] 
Ahn MJ, Sun JM, Lee SH, Ahn JS, Park K. EGFR TKI combination with immunotherapy in non-small cell lung cancer. Expert Opin Drug Saf  2017; 16(4): 465-9.
[http://dx.doi.org/10.1080/14740338.2017.1300656] [PMID: 28271729] 
[97] 
Lacouture M, Sibaud V. Toxic side effects of targeted therapies and immunotherapies affecting the skin, oral mucosa, hair, and nails. Am J Clin Dermatol  2018; 19(Suppl. 1): 31-9.
[http://dx.doi.org/10.1007/s40257-018-0384-3] [PMID: 30374901] 
[98] 
Yang S, Zhang W, Chen Q, Guo Q. Clinical investigation of the efficacy and safety of anlotinib with immunotherapy in advanced non-small cell lung cancer as third-line therapy: A retrospective study. Cancer Manag Res  2020; 12: 10333-40.
[http://dx.doi.org/10.2147/CMAR.S280096] [PMID: 33116888] 
[99] 
Kim JJ, Vaziri SA, Rini BI, et al. Association of VEGF and VEGFR2 single nucleotide polymorphisms with hypertension and clinical outcome in metastatic clear cell renal cell carcinoma patients treated with sunitinib. Cancer  2012; 118(7): 1946-54.
[http://dx.doi.org/10.1002/cncr.26491] [PMID: 21882181] 
[100] 
Garcia-Donas J, Esteban E, Leandro-García LJ, et al. Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal-cell carcinoma treated with first-line sunitinib: A multicentre, observational, prospective study. Lancet Oncol  2011; 12(12): 1143-50.
[http://dx.doi.org/10.1016/S1470-2045(11)70266-2] [PMID: 22015057] 
Rights & Permissions Print Cite
Article Metrics
43
2
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1381612827666211006145141	Print ISSN 1381-6128
Publisher Name Bentham Science Publisher	Online ISSN 1873-4286
Current Pharmaceutical Design

Anlotinib-Induced Hypertension: Current Concepts and Future Prospects

Abstract Play Pause

Related Journals

Related Books

Related Articles

Abstract
