Investigation of drugs affecting hypertension in bevacizumab-treated patients and examination of the impact on the therapeutic effect.

Publisher: John Wiley & Sons Ltd Country of Publication: United States NLM ID: 101595310 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2045-7634 (Electronic) Linking ISSN: 20457634 NLM ISO Abbreviation: Cancer Med Subsets: MEDLINE

Original Publication: [Malden, MA] : John Wiley & Sons Ltd., c2012-

Angiogenesis Inhibitors/*adverse effects ; Antihypertensive Agents/*therapeutic use ; Antineoplastic Agents, Immunological/*adverse effects ; Bevacizumab/*adverse effects ; Blood Pressure/*drug effects ; Colorectal Neoplasms/*drug therapy ; Hypertension/*prevention & control ; Proton Pump Inhibitors/*therapeutic use; Adult ; Adverse Drug Reaction Reporting Systems ; Aged ; Aged, 80 and over ; Antihypertensive Agents/adverse effects ; Cell Line, Tumor ; Colorectal Neoplasms/metabolism ; Databases, Factual ; Drug Interactions ; Female ; Human Umbilical Vein Endothelial Cells/drug effects ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; Hypertension/chemically induced ; Hypertension/diagnosis ; Hypertension/physiopathology ; Japan ; Male ; Middle Aged ; Proton Pump Inhibitors/adverse effects ; Retrospective Studies ; Treatment Outcome ; United States ; United States Food and Drug Administration ; Up-Regulation ; Vascular Endothelial Growth Factor A/metabolism

Background: In patients treated with bevacizumab, hypertension may be a biomarker of therapeutic efficacy. However, it is not clear whether drugs that control blood pressure influence bevacizumab's efficacy. In this study, we investigated drugs that may affect hypertension in bevacizumab-treated patients and examined the impact on the therapeutic effect.
Patients and Methods: We analyzed 3,724,555 reports from the third quarter of 2010 to the second quarter of 2015. All data were obtained from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) analysis. In this retrospective cohort study, we investigated a total of 58 patients diagnosed with colorectal cancer and treated for the first time with bevacizumab containing XELOX or mFOLFOX6 at The University of Tokushima Hospital between January 2010 and December 2015. The effect of the treatment was evaluated according to Response Evaluation Criteria in Solid Tumors version 1.0. Thereafter, the effect was confirmed using Gene Expression Omnibus (GEO) and cultured cells.
Results: There are few reports in FAERS of hypertension in patients treated with omeprazole on bevacizumab. Based on the chart review, patients who used proton pump inhibitors (PPI) had a lower response to treatment than those who did not (response rate: 25% vs 50%). Furthermore, experiments on GEO and cell lines suggested that induction of vascular endothelial growth factor (VEGF) gene expression by PPIs is the cause of the reduced therapeutic effect.
Conclusion: PPIs prevent hypertension in bevacizumab-treated patients but may reduce bevacizumab's anti-tumoral effects by inducing VEGF expression.
(© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

PLoS One. 2015 Sep 02;10(9):e0136324. (PMID: 26331473)
Eur J Cancer. 2017 Jan;70:146-155. (PMID: 27817944)
PLoS One. 2014 Feb 18;9(2):e89150. (PMID: 24558482)
ESMO Open. 2016 May 17;1(3):e000045. (PMID: 27843607)
Br J Cancer. 2011 Feb 15;104(4):599-604. (PMID: 21304526)
Sci Transl Med. 2013 Oct 9;5(206):206ra140. (PMID: 24107779)
BMJ Open. 2017 Oct 30;7(10):e017739. (PMID: 29084798)
Med Oncol. 2013 Mar;30(1):327. (PMID: 23254964)
N Engl J Med. 2006 Dec 14;355(24):2542-50. (PMID: 17167137)
Nucleic Acids Res. 2002 Jan 1;30(1):207-10. (PMID: 11752295)
J Clin Oncol. 2008 Jul 20;26(21):3523-9. (PMID: 18640933)
Front Pharmacol. 2019 Nov 08;10:1257. (PMID: 31780928)
Oncol Lett. 2018 Jul;16(1):27-33. (PMID: 29928383)
Yakugaku Zasshi. 2011;131(8):1251-7. (PMID: 21804330)
Thorac Cancer. 2020 Jul;11(7):1763-1764. (PMID: 32374445)
Cancer Chemother Pharmacol. 2011 Nov;68(5):1207-13. (PMID: 21409384)
Cancer Med. 2019 Jan;8(1):174-181. (PMID: 30561126)
Ann Oncol. 2020 Apr;31(4):525-531. (PMID: 32115349)
J Clin Pharm Ther. 2018 Feb;43(1):65-72. (PMID: 28895169)
Sci Rep. 2016 May 20;6:26375. (PMID: 27199286)
Gynecol Oncol Rep. 2016 Jun 16;17:65-8. (PMID: 27617286)
J Am Soc Hypertens. 2018 Jun;12(6):409-425. (PMID: 29703600)
Br J Cancer. 2019 Jul;121(2):109-116. (PMID: 31182765)
Oncol Rep. 2017 Jan;37(1):601-607. (PMID: 27840995)
Hypertension. 2009 Sep;54(3):652-8. (PMID: 19652084)
J Hypertens. 2019 Jan;37(1):73-83. (PMID: 30303488)
Front Oncol. 2020 Feb 27;10:221. (PMID: 32175278)
Pharmacoepidemiol Drug Saf. 2002 Jan-Feb;11(1):3-10. (PMID: 11998548)
Cancers (Basel). 2020 Mar 10;12(3):. (PMID: 32164284)
Nucleic Acids Res. 2000 Jan 1;28(1):27-30. (PMID: 10592173)
Lancet Oncol. 2013 Jan;14(1):29-37. (PMID: 23168366)
Gut. 2018 Jan;67(1):28-35. (PMID: 29089382)
J Hosp Med. 2012 May-Jun;7(5):421-5. (PMID: 22190465)

Keywords: FAERS; bevacizumab; colorectal cancer; gene expression omnibus; hypertension; proton pump inhibitor

0 (Angiogenesis Inhibitors)
0 (Antihypertensive Agents)
0 (Antineoplastic Agents, Immunological)
0 (Proton Pump Inhibitors)
0 (VEGFA protein, human)
0 (Vascular Endothelial Growth Factor A)
2S9ZZM9Q9V (Bevacizumab)

Date Created: 20201124 Date Completed: 20210720 Latest Revision: 20210720

20250114

PMC7826469

10.1002/cam4.3587

33231381