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Plasma levels of VEGF-A and VCAM-1 as predictors of drug-induced hypertension in patients treated with VEGF pathway inhibitors.

Publication ,  Journal Article
Quintanilha, JCF; Hammond, K; Liu, Y; Marmorino, F; Borelli, B; Cremolini, C; Nixon, AB; Innocenti, F
Published in: Br J Clin Pharmacol
September 2022

AIMS: Hypertension is a common toxicity induced by vascular endothelial growth factor (VEGF) pathway inhibitors. There are no validated markers of hypertension induced by these drugs. METHODS: We previously discovered that cancer patients with lower plasma levels of angiopoietin-2, VCAM-1 and VEGF-A are at high risk of developing severe hypertension when treated with bevacizumab. This study aimed to validate the predictive value of these markers in pretreatment plasma samples of an additional cohort of 101 colorectal cancer patients treated with regorafenib. The levels of angiopoietin-2, VCAM-1 and VEGF-A were measured by enzyme-linked immunosorbent assay (ELISA). The association between proteins and grade ≥2 regorafenib-induced hypertension was performed by calculating the odds ratio (OR) from logistic regression. Using the optimal cut-point of each protein, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for hypertension were estimated. RESULTS: Lower levels of VCAM-1 (P = .015, OR = 3.11, 95% CI 1.27-8.08) and VEGF-A (P = .007, OR = 3.47, 95% CI 1.40-8.75) were associated with a higher risk of hypertension. Levels of angiopoietin-2 were not associated with hypertension. The multivariable model indicates an independent effect of VCAM-1 (P = .018, OR = 3.18, 95% CI 1.25-8.68) and VEGF-A (P = .008, OR = 3.77, 95% CI 1.44-10.21). The presence of low levels of both VCAM-1 and VEGF-A had an OR of 9.46 (95% CI 3.08-33.26, P = 1.70 × 10-4 ) for the risk of hypertension (sensitivity of 41.4%, specificity of 93.1%, PPV of 70.6% and NPV of 79.8%). CONCLUSIONS: This study confirmed the value of VCAM-1 and VEGF-A levels in predicting hypertension induced by regorafenib, another VEGF pathway inhibitor.

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Published In

Br J Clin Pharmacol

DOI

EISSN

1365-2125

Publication Date

September 2022

Volume

88

Issue

9

Start / End Page

4171 / 4179

Location

England

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Vascular Cell Adhesion Molecule-1
  • Pharmacology & Pharmacy
  • Hypertension
  • Humans
  • Angiopoietin-2
  • Angiogenesis Inhibitors
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences
 

Citation

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Quintanilha, J. C. F., Hammond, K., Liu, Y., Marmorino, F., Borelli, B., Cremolini, C., … Innocenti, F. (2022). Plasma levels of VEGF-A and VCAM-1 as predictors of drug-induced hypertension in patients treated with VEGF pathway inhibitors. Br J Clin Pharmacol, 88(9), 4171–4179. https://doi.org/10.1111/bcp.15356
Quintanilha, Julia C. F., Kelli Hammond, Yingmiao Liu, Federica Marmorino, Beatrice Borelli, Chiara Cremolini, Andrew B. Nixon, and Federico Innocenti. “Plasma levels of VEGF-A and VCAM-1 as predictors of drug-induced hypertension in patients treated with VEGF pathway inhibitors.Br J Clin Pharmacol 88, no. 9 (September 2022): 4171–79. https://doi.org/10.1111/bcp.15356.
Quintanilha JCF, Hammond K, Liu Y, Marmorino F, Borelli B, Cremolini C, et al. Plasma levels of VEGF-A and VCAM-1 as predictors of drug-induced hypertension in patients treated with VEGF pathway inhibitors. Br J Clin Pharmacol. 2022 Sep;88(9):4171–9.
Quintanilha, Julia C. F., et al. “Plasma levels of VEGF-A and VCAM-1 as predictors of drug-induced hypertension in patients treated with VEGF pathway inhibitors.Br J Clin Pharmacol, vol. 88, no. 9, Sept. 2022, pp. 4171–79. Pubmed, doi:10.1111/bcp.15356.
Quintanilha JCF, Hammond K, Liu Y, Marmorino F, Borelli B, Cremolini C, Nixon AB, Innocenti F. Plasma levels of VEGF-A and VCAM-1 as predictors of drug-induced hypertension in patients treated with VEGF pathway inhibitors. Br J Clin Pharmacol. 2022 Sep;88(9):4171–4179.
Journal cover image

Published In

Br J Clin Pharmacol

DOI

EISSN

1365-2125

Publication Date

September 2022

Volume

88

Issue

9

Start / End Page

4171 / 4179

Location

England

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Vascular Cell Adhesion Molecule-1
  • Pharmacology & Pharmacy
  • Hypertension
  • Humans
  • Angiopoietin-2
  • Angiogenesis Inhibitors
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences