外科理论与实践 ›› 2020, Vol. 25 ›› Issue (01): 29-34.doi: 10.16139/j.1007-9610.2020.01.007
收稿日期:
2019-10-25
出版日期:
2020-01-25
发布日期:
2020-02-25
通讯作者:
张倜
E-mail:zhangti@tjmuch.com
基金资助:
Received:
2019-10-25
Online:
2020-01-25
Published:
2020-02-25
Contact:
ZHANG Ti
E-mail:zhangti@tjmuch.com
中图分类号:
张倜, 杨雪娇. 肝癌靶向治疗相关高血压的发生与处置[J]. 外科理论与实践, 2020, 25(01): 29-34.
ZHANG Ti, YANG Xuejiao. Occurrence and treatment of hypertension associated with targeted therapy in hepatocellular carcinoma[J]. Journal of Surgery Concepts & Practice, 2020, 25(01): 29-34.
表1
VEGF抑制剂治疗肿瘤的机制、靶点及高血压发生率
药物 | 机制 | 靶点 | 所有高血压(%) | 中、重度高血压(%) |
---|---|---|---|---|
索拉非尼[ | TKI | VEGFR2-3, Raf-1, B-Raf | 18.8 | 2 |
瑞戈非尼[ | TKI | VEGFR1-3, PDGFR, c-kit, RET, Raf-1 | 31 | 15 |
伦伐替尼[ | TKI | VEGFR1-3, FGFR1-4, PDGFR, c-kit, RET | 42 | 23 |
卡博替尼[ | TKI | MET, VEGFR2, RET, AXL, FLT3 | 29 | 16.3 |
布立尼布[ | TKI | VEGFR,FGFR | 27 | 5.3 |
利尼伐尼[ | TKI | VEGFR, PDGFR | 20.8 | - |
舒尼替尼[ | TKI | VEGFR2, PDGFR, c-kit | 20.9 | 3.8 |
多韦替尼[ | TKI | VEGFR, PDGFR | 22 | 13 |
阿昔替尼[ | TKI | VEGFR1-3, c-kit, PDGFR | 54 | 26 |
西地尼布[ | TKI | VEGFR1-3,PDGFR | 41 | 29 |
雷莫芦单抗[ | IgG1 | VEGF | 25 | 13 |
贝伐单抗[ | IgG1 | VEGFR2 | 33 | 15 |
表2
药物相关性高血压的治疗
项目 | 药物类别 | 代表药物 | 注意事项 |
---|---|---|---|
首选 | 二氢砒啶类CCB | 氨氯地平 非洛地平 (除外硝苯地平) | 腿部肿胀 起效缓慢 |
ARB | 缬沙坦 氯沙坦 厄贝沙坦 坎地沙坦 | 肾血管疾病 周边血管疾病肾功能不全 肾脏化学疗法间隙 高钾血症 | |
次选 | 利尿剂 | 螺内酯 氢氯噻嗪 | 痛风 高钾血症 低钾血症 QTc延长药 |
β受体阻滞剂 | 比索洛尔 美托洛尔 | 心动过缓 心脏传导阻滞 哮喘或慢阻肺 | |
避免使用 | 非二氢吡啶类CCB | 维拉帕米 地尔硫卓 | 影响VEGF抑制剂血药浓度 |
ACEI | 卡托普利 依那普利 培哚普利 | 促进肿瘤生长 | |
血压监测 | 停止降压治疗后定期监测有无反弹性低血压 VEGF抑制剂停止应用或减量后定期监测血压 | ||
可发展药物 | NO供体 | 莫斯多明 硝酸异山梨酯或单硝酸异山梨酯 西地那非 | |
ET-1抑制剂 | 马西替坦 |
[1] |
Greten TF, Lai CW, Li G, et al. Targeted and immune-based therapies for hepatocellular carcinoma[J]. Gastroenterology, 2019, 156(2):510-524.
doi: S0016-5085(18)35082-0 pmid: 30287171 |
[2] | Pan Z, Zhuang J, Ji C, et al. Curcumin inhibits hepatocellular carcinoma growth by targeting VEGF expression[J]. Oncol Lett, 2018, 15(4):4821-4826. |
[3] |
Duffaud F, Sleijfer S, Litiere S, et al. Hypertension (HTN) as a potential biomarker of efficacy in pazopanib-treated patients with advanced non-adipocytic soft tissue sarcoma. A retrospective study based on European Organisation for Research and Treatment of Cancer (EORTC) 62043 and 62072 trials[J]. Eur J Cancer, 2015, 51(17):2615-2623.
doi: 10.1016/j.ejca.2015.08.002 pmid: 26321011 |
[4] |
Gensicka M, Glowacka A, Dzierzbicka K, et al. Inhibitors of angiogenesis in cancer therapy-synthesis and biological activity[J]. Curr Med Chem, 2015, 22(33):3830-3847.
pmid: 26337104 |
[5] |
Shigeta K, Datta M, Hato T, et al. Dual programmed death receptor-1 and vascular endothelial growth factor receptor-2 blockade promotes vascular normalization and enhances antitumor immune responses in hepatocellular carcinoma[J]. Hepatology, 2019,doi: 10.1002/hep.30889.
doi: 10.1002/hep.30889 URL |
[6] | Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma[J]. N Engl J Med, 2008, 359(4):378-390. |
[7] | 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[J]. Lancet, 2017, 389(10064):56-66. |
[8] | Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial[J]. Lancet, 2018, 391(10126):1163-1173. |
[9] | Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma[J]. N Engl J Med, 2018, 379(1):54-63. |
[10] |
Johnson PJ, Qin S, Park JW, et al. Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomized phase Ⅲ BRISK-FL study[J]. J Clin Oncol, 2013, 31(28):3517-3524.
doi: 10.1200/JCO.2012.48.4410 pmid: 23980084 |
[11] |
Cainap C, Qin S, Huang WT, et al. Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma: results of a randomized phase Ⅲ trial[J]. J Clin Oncol, 2015, 33(2):172-179.
doi: 10.1200/JCO.2013.54.3298 pmid: 25488963 |
[12] | Cheng AL, Kang YK, Lin DY, et al. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase Ⅲ trial[J]. J Clin Oncol, 2013, 31(32):4067-4075. |
[13] | Cheng AL, Thongprasert S, Lim HY, et al. Randomized, open-label phase 2 study comparing frontline dovitinib versus sorafenib in patients with advanced hepatocellular carcinoma[J]. Hepatology, 2016, 64(3):774-784. |
[14] |
Kang YK, Yau T, Park JW, et al. Randomized phase Ⅱ study of axitinib versus placebo plus best supportive care in second-line treatment of advanced hepatocellular carcinoma[J]. Ann Oncol, 2015, 26(12):2457-2463.
doi: 10.1093/annonc/mdv388 pmid: 26386123 |
[15] | Zhu AX, Ancukiewicz M, Supko JG, et al. Efficacy, safety, pharmacokinetics, and biomarkers of cediranib monotherapy in advanced hepatocellular carcinoma: a phase Ⅱ study[J]. Clin Cancer Res, 2013, 19(6):1557-1566. |
[16] | Zhu AX, Kang YK, Yen CJ, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased alpha-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet Oncol, 2019, 20(2):282-296. |
[17] |
Siegel AB, Cohen EI, Ocean A, et al. Phase Ⅱ trial eva-luating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma[J]. J Clin Oncol, 2008, 26(18):2992-2998.
doi: 10.1200/JCO.2007.15.9947 pmid: 18565886 |
[18] | Azizi M, Chedid A, Oudard S. Home blood-pressure mo-nitoring in patients receiving sunitinib[J]. N Engl J Med, 2008, 358(1):95-97. |
[19] | Kappers MH, van Esch JH, Sluiter W, et al. Hypertension induced by the tyrosine kinase inhibitor sunitinib is associated with increased circulating endothelin-1 levels[J]. Hypertension, 2010, 56(4):675-681. |
[20] | Lankhorst S, Baelde HJ, Clahsen-van Groningen MC, et al. Effect of high salt diet on blood pressure and renal damage during vascular endothelial growth factor inhibition with sunitinib[J]. Nephrol Dial Transplant, 2016, 31(6):914-921. |
[21] | Hamnvik OP, Choueiri TK, Turchin A, et al. Clinical risk factors for the development of hypertension in patients treated with inhibitors of the VEGF signaling pathway[J]. Cancer, 2015, 121(2):311-319. |
[22] |
Abdel-Qadir H, Ethier JL, Lee DS, et al. Cardiovascular toxicity of angiogenesis inhibitors in treatment of malignancy: A systematic review and meta-analysis[J]. Cancer Treat Rev, 2017, 53:120-127.
doi: S0305-7372(16)30143-8 pmid: 28104567 |
[23] | Carter JJ, Fretwell LV, Woolard J. Effects of 4 multitargeted receptor tyrosine kinase inhibitors on regional hemodynamics in conscious, freely moving rats[J]. FASEB J, 2017, 31(3):1193-1203. |
[24] | Mohammadzadeh M, Halabian R, Gharehbaghian A, et al. Nrf-2 overexpression in mesenchymal stem cells reduces oxidative stress-induced apoptosis and cytotoxicity[J]. Cell Stress Chaperones, 2012, 17(5):553-565. |
[25] |
Verdonk K, Saleh L, Lankhorst S, et al. Association stu-dies suggest a key role for endothelin-1 in the pathogene-sis of preeclampsia and the accompanying renin-angiotensin-aldosterone system suppression[J]. Hypertension, 2015, 65(6):1316-1323.
doi: 10.1161/HYPERTENSIONAHA.115.05267 pmid: 25870197 |
[26] |
de Jesus-Gonzalez N, Robinson E, Moslehi J, et al. Ma-nagement of antiangiogenic therapy-induced hypertension[J]. Hypertension, 2012, 60(3):607-615.
doi: 10.1161/HYPERTENSIONAHA.112.196774 pmid: 22851729 |
[27] |
Gennari-Moser C, Khankin EV, Escher G, et al. Vascular endothelial growth factor-A and aldosterone: relevance to normal pregnancy and preeclampsia[J]. Hypertension, 2013, 61(5):1111-1117.
doi: 10.1161/HYPERTENSIONAHA.111.00575 pmid: 23460276 |
[28] | Serne EH, Gans RO ter Maaten JC, et al. Impaired skin capillary recruitment in essential hypertension is caused by both functional and structural capillary rarefaction[J]. Hypertension, 2001, 38(2):238-242. |
[29] | Wiig H, Schröder A, Neuhofer W, et al. Immune cells control skin lymphatic electrolyte homeostasis and blood pressure[J]. J Clin Invest, 2013, 123(7):2803-2815. |
[30] |
Selvarajah V, Mäki-Petaja KM, Pedro L, et al. Novel mechanism for buffering dietary salt in humans: effects of salt loading on skin sodium, vascular endothelial growth factor C, and blood pressure[J]. Hypertension, 2017, 70(5):930-937.
doi: 10.1161/HYPERTENSIONAHA.117.10003 pmid: 28974570 |
[31] |
Langenberg MH, van Herpen CM, De Bono J, et al. Effective strategies for management of hypertension after vascular endothelial growth factor signaling inhibition therapy: results from a phase Ⅱ randomized, factorial, double-blind study of Cediranib in patients with advanced solid tumors[J]. J Clin Oncol, 2009, 27(36):6152-6159.
doi: 10.1200/JCO.2009.22.2273 pmid: 19901116 |
[32] |
Zamorano JL, Lancellotti P, Rodriguez Munoz D, et al. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology(ESC)[J]. Eur Heart J, 2016, 37(36):2768-2801.
doi: 10.1093/eurheartj/ehw211 pmid: 27567406 |
[33] |
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]. J Natl Cancer Inst, 2010, 102(9):596-604.
doi: 10.1093/jnci/djq091 pmid: 20351338 |
[34] | Caletti S, Paini A, Coschignano MA, et al. Management of VEGF-Targeted therapy-induced hypertension[J]. Curr Hypertens Rep, 2018, 20(8):68. |
[35] |
Derosa L, Izzedine H, Albiges L, et al. Hypertension and angiotensin system inhibitors in patients with metastatic renal cell carcinoma[J]. Oncol Rev, 2016, 10(2):298.
pmid: 27994768 |
[36] |
Izzedine H, Ederhy S, Goldwasser F, et al. Management of hypertension in angiogenesis inhibitor-treated patients[J]. Ann Oncol, 2009, 20(5):807-815.
doi: 10.1093/annonc/mdn713 pmid: 19150949 |
[37] |
Ishikane S, Takahashi-Yanaga F. The role of angiotensin Ⅱ in cancer metastasis: Potential of renin-angiotensin system blockade as a treatment for cancer metastasis[J]. Biochem Pharmacol, 2018, 151:96-103.
doi: S0006-2952(18)30105-9 pmid: 29534876 |
[38] | Lankhorst S, Kappers MH, van Esch JH, et al. Treatment of hypertension and renal injury induced by the angiogenesis inhibitor sunitinib: preclinical study[J]. Hypertension, 2014, 64(6):1282-1289. |
[39] | Liu Y, Li B, Wang X, et al. Angiotensin-(1-7) suppresses hepatocellular carcinoma growth and angiogenesis via complex interactions of angiotensin Ⅱ type 1 receptor, angiotensin Ⅱ type 2 receptor and mas receptor[J]. Mol Med, 2015, 21:626-636. |
[40] | Andoh T, Akira A, Saiki I, et al. Bradykinin increases the secretion and expression of endothelin-1 through kinin B2 receptors in melanoma cells[J]. Peptides, 2010, 31(2):238-241. |
[41] | Pasquier E, Street J, Pouchy C, et al. β-blockers increase response to chemotherapy via direct antitumour and anti-angiogenic mechanisms in neuroblastoma[J]. Br J Cancer, 2013, 108(12):2485-2494. |
[42] |
Kruzliak P, Novák J, Novák M. Vascular endothelial growth factor inhibitor-induced hypertension: from pathophysiology to prevention and treatment based on lon-gacting nitric oxide donors[J]. Am J Hypertens, 2014, 27(1):3-13.
doi: 10.1093/ajh/hpt201 pmid: 24168915 |
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