The effect of concomitant beta-blocker use on survival in patients with metastatic renal cell carcinoma treated with a vascular endothelial growth factor receptor inhibitors in the first line.

Beta-blocker Pazopanib Renal cell carcinoma Sunitinib

Journal

European journal of clinical pharmacology
ISSN: 1432-1041
Titre abrégé: Eur J Clin Pharmacol
Pays: Germany
ID NLM: 1256165

Informations de publication

Date de publication:
13 Mar 2024
Historique:
received: 12 06 2023
accepted: 06 03 2024
medline: 13 3 2024
pubmed: 13 3 2024
entrez: 13 3 2024
Statut: aheadofprint

Résumé

Vascular endothelial growth factor (VEGF) inhibition is one of the cornerstones of treatment in the treatment of metastatic renal cell carcinoma (mRCC). Since RCC is a disease of advanced age and hypertension as a side effect of VEGF receptor inhibitors, beta-blocker use is common in these patients. We aimed to compare the treatment efficacy and survival results in case of concomitant use of these two drugs due to the inhibition of VEGF in beta-blockers. A total of 121 patients with a diagnosis of mRCC who used sunitinib or pazopanib in first-line therapy were included in the study. These patients were divided into two groups as those using concomitant beta-blockers and those not using them. The median overall survival (mOS) of the patient using sunitinib or pazopanib and concomitant beta-blocker was 47 (95% CI 29.0-65.0) months, and the mOS of those not using concomitant beta-blocker was 18 (95% CI 8.9-27.1) months (p < 0.001). The median progression-free survival (mPFS) of the patients using sunitinib or pazopanib and concomitant beta-blocker was 20.4 (95% CI 4.5-40.1) months, and the mPFS of those not using it was 11.4 (95% CI 5.9-16.9) months (p = 0.042). Concomitant beta-blocker use was found to be a good prognostic factor for OS in the multivariate analysis (p = 0.029). In the multivariate analysis, concomitant beta-blocker use had a trend towards statistical significance for PFS (p = 0.062). Concomitant use of betablockers with sunitinib or pazopanib is associated with longer overall survial and progression free survival.

Identifiants

pubmed: 38478093
doi: 10.1007/s00228-024-03668-8
pii: 10.1007/s00228-024-03668-8
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Références

Siegel RL, Miller KA, Wagle NS, Jemal A (2023) Cancer statistics, 2023. CA A Cancer J Clin 73(1):17–48
doi: 10.3322/caac.21763
Garfield K, LaGrange CA (2024) Renal Cell Cancer. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing
Padala SA, Barsouk A, Thandra KC, Saginala K, Mohammed A, Vakiti A, Rawla P, Barsouk A (2020) Epidemiology of renal cell carcinoma. World J Oncol 11(3):79–87
doi: 10.14740/wjon1279 pubmed: 32494314 pmcid: 7239575
McDermott DF, Regan MM, Clark JI et al (2005) Randomized phase III trial of high-dose interleukin-2 versus subcutaneous ınterleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol 23(1):133–141
doi: 10.1200/JCO.2005.03.206 pubmed: 15625368
Motzer RJ, Hutson TE, Cella D et al (2013) Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med 369(8):722–731
doi: 10.1056/NEJMoa1303989 pubmed: 23964934
Simons M, Gordon E, Claesson-Welsh L (2016) Mechanisms and regulation of endothelial VEGF receptor signalling. Nat Rev Mol Cell Biol 17(10):611–625
doi: 10.1038/nrm.2016.87 pubmed: 27461391
Steeghs N, Gelderblom H, Roodt JO, Christensen O, Rajagopalan P, Hovens MMC, Putter H, Rabelink TJ, De Koning EJ (2008) Hypertension and rarefaction during treatment with telatinib, a small molecule angiogenesis ınhibitor. Clin Cancer Res 14(11):3470–3476
doi: 10.1158/1078-0432.CCR-07-5050 pubmed: 18519779
Rini BI, Small EJ (2005) Biology and clinical development of vascular endothelial growth factor–targeted therapy in renal cell carcinoma. J Clin Oncol 23(5):1028–1043
doi: 10.1200/JCO.2005.01.186 pubmed: 15534359
Rini BI, Cohen D, Lu DR, Chen I, Hariharan S, Gore M, Figlin RA, Baum MJ, Motzer RJ (2011) Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst 103(9):763–773
doi: 10.1093/jnci/djr128 pubmed: 21527770 pmcid: 3086879
Verheul HM, Pinedo HM (2007) Possible molecular mechanisms involved in the toxicity of angiogenesis inhibition. Nat Rev Cancer 7(6):475–485
doi: 10.1038/nrc2152 pubmed: 17522716
Ba Z, Xiao Y, He M, Liu D, Wang H, Liang H, Yuan J (2022) Risk factors for the comorbidity of hypertension and renal cell carcinoma in the cardio-oncologic era and treatment for tumor-induced hypertension. Front Cardiovasc Med 9:810262
doi: 10.3389/fcvm.2022.810262 pubmed: 35252390 pmcid: 8892205
Shah S, Harris T, Owen CG, DeWilde S, Cook DG (2011) Does β-adrenoceptor blocker therapy improve cancer survival? Findings from a population-based retrospective cohort study. Br J Clin Pharmacol 72(1):157–161
doi: 10.1111/j.1365-2125.2011.03980.x pubmed: 21453301 pmcid: 3141198
Na Z, Qiao X, Hao X, Fan L, Xiao Y, Shao Y, Sun M, Feng Z, Guo W, Li J, Li J, Li D (2018) The effects of beta-blocker use on cancer prognosis: a meta-analysis based on 319,006 patients. Onco Targets Ther 11:4913–4944
doi: 10.2147/OTT.S167422 pubmed: 30174436 pmcid: 6109661
Parker W, Lohse CM, Zaid HB, Cheville JC, Boorjian SA, Leibovich BC, Thompson RH (2017) Evaluation of beta-blockers and survival among hypertensive patients with renal cell carcinoma. Urologic Oncology-seminars and Original Investigations 35(1):36.e1-36
doi: 10.1016/j.urolonc.2016.08.013
Neumann E, Klaiber P, Freitag K, Schwab M, Schaeffeler E, Hennenlotter J, Fend F, Kruck S, Scharpf M, Stenzl A, Bedke J, Rausch S (2019) Assessment of concomitant non-oncologic medication in patients with surgically treated renal cell carcinoma: impact on prognosis, cell-cycle progression and proliferation. J Cancer Res Clin Oncol 145(7):1835–1843
doi: 10.1007/s00432-019-02914-2 pubmed: 31006846
Babiak-Choroszczak L, Giżewska-Kacprzak K, Gawrych E, Fischer K, Walecka A, Puchalska-Niedbał L, Rajewska-Majchrzak J, Bagłaj M (2018) Serum concentrations of VEGF and bFGF in the course of propranolol therapy of infantile hemangioma in children: are we closer to understand the mechanism of action of propranolol on hemangiomas? Adv Clin Exp Med 27(5):703–710
doi: 10.17219/acem/84800 pubmed: 29790692
Shahzad MM, Arevalo JM, Armaiz-Pena GN, Lu C, Stone RL, Moreno-Smith M, Nishimura M, Lee J, Jennings NR, Bottsford-Miller J, Vivas-Mejia PE, Lutgendorf SK, Lopez-Berestein G, Bar-Eli M, Cole SW, Sood AK (2010) Stress effects on FosB- and interleukin-8 (IL8)-driven ovarian cancer growth and metastasis. J Biol Chem 285(46):35462–35470
doi: 10.1074/jbc.M110.109579 pubmed: 20826776 pmcid: 2975170
Zhong S, Yu D, Zhang X, Chen X, Yang S, Tang J, Zhao J, Wang S (2016) β-Blocker use and mortality in cancer patients: systematic review and meta-analysis of observational studies. Eur J Cancer Prev 25(5):440–448
doi: 10.1097/CEJ.0000000000000192 pubmed: 26340056
Kocak MZ, Er M, Ugrakli M, Hendem E, Araz M, Eryilmaz MK, Artac M (2023) Could the concomitant use of beta blockers with bevacizumab improve survival in metastatic colon cancer? Eur J Clin Pharmacol 79(4):485–491
doi: 10.1007/s00228-023-03464-w pubmed: 36749352
Fiala O, Ostasov P, Sorejs O, Liska V, Buchler T, Poprach A, Finek J (2019) Incidental use of beta-blockers ıs associated with outcome of metastatic colorectal cancer patients treated with bevacizumab-based therapy: a single-ınstitution retrospective analysis of 514 patients. Cancers 11(12):1856
doi: 10.3390/cancers11121856 pubmed: 31769417 pmcid: 6966537
Giampieri R, Scartozzi M, Del Prete M, Faloppi L, Bianconi M, Ridolfi F, Cascinu S (2015) Prognostic value for incidental antihypertensive therapy with β-blockers in metastatic colorectal cancer. Med 94(24):e719
doi: 10.1097/MD.0000000000000719
Fiala O, Ostasov P, Rozsypalova A, Hora M, Šorejs O, Šustr J, Bendová B, Trávníček I, Filipovský J, Fínek J, Buchler T (2021) Impact of concomitant cardiovascular medication on survival of metastatic renal cell carcinoma patients treated with sunitinib or pazopanib in the first line. Target Oncol 16(5):643–652
doi: 10.1007/s11523-021-00829-y pubmed: 34363554

Auteurs

Mustafa Korkmaz (M)

Department of Medical Oncology, Necmettin Erbakan University School of Medicine, Konya, 42080, Turkey. dr.musstafa@gmail.com.

Melek Karakurt Eryılmaz (MK)

Department of Medical Oncology, Necmettin Erbakan University School of Medicine, Konya, 42080, Turkey.

Mehmet Zahid Koçak (MZ)

Department of Medical Oncology, Necmettin Erbakan University School of Medicine, Konya, 42080, Turkey.

Muhammed Muhiddin Er (MM)

Department of Medical Oncology, Necmettin Erbakan University School of Medicine, Konya, 42080, Turkey.

Engin Hendem (E)

Department of Medical Oncology, Necmettin Erbakan University School of Medicine, Konya, 42080, Turkey.

Aykut Demirkıran (A)

Department of Medical Oncology, Necmettin Erbakan University School of Medicine, Konya, 42080, Turkey.

Murat Araz (M)

Department of Medical Oncology, Necmettin Erbakan University School of Medicine, Konya, 42080, Turkey.

Mehmet Artaç (M)

Department of Medical Oncology, Necmettin Erbakan University School of Medicine, Konya, 42080, Turkey.

Classifications MeSH