Could the concomitant use of beta blockers with bevacizumab improve survival in metastatic colon cancer?

Eur J Clin Pharmacol. 2023 Apr;79(4):485-491. doi: 10.1007/s00228-023-03464-w. Epub 2023 Feb 7.

Abstract

Aim: Drug-drug interactions are sometimes neglected in oncology practice. Due to drug pharmacokinetic and pharmacodynamic interactions, clinically increased or decreased drug effects and increased or decreased adverse effects may occur. Considering that the concomitant use of these two drugs that affect vascular endothelial growth factor receptor (VEGFR) may cause pharmacological potentiation or additive interaction, we aimed to evaluate the survival outcomes of concomitant use of bevacizumab and beta blockers in patients with metastatic colorectal cancer (mCRC).

Methods: In total, 181 patients with mCRC administered with bevacizumab plus cytotoxic chemotherapy regimen in a first-line setting were divided into two groups: concomitant beta-blocker user and nonuser.

Results: The median overall survival (mOS) was 35.9 (95% CI: 27.9-43.9) months in the beta-blocker-using group and 29.6 (95% CI: 27.9-43.9) months in the beta-blocker-non-using group (p = 0.054). The median progression-free survival (mPFS) was 16.1 (95% CI: 12.4-19.9) months in the beta-blocker-using group and 12.8 (95% CI: 10.6-15.0) months in the beta-blocker-non-using group (p = 0.006). The multivariate analysis revealed that beta-blocker use was an independent predictor of mPFS (HR: 0.66, 95% CI: 0.46-0.93, p = 0.018) and mOS (HR: 0.57, 95% CI: 0.36-0.91, p = 0.02).

Conclusion: This study demonstrated that concomitant usage of beta blockers improved both survival outcomes, irrespective of the kind of beta blocker.

Keywords: Beta blocker; Bevacizumab; Colon cancer; Metastasis.

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab / adverse effects
  • Colonic Neoplasms* / drug therapy
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / pathology
  • Disease-Free Survival
  • Fluorouracil / therapeutic use
  • Humans
  • Rectal Neoplasms* / drug therapy
  • Vascular Endothelial Growth Factor A / therapeutic use

Substances

  • Bevacizumab
  • Vascular Endothelial Growth Factor A
  • Adrenergic beta-Antagonists
  • Fluorouracil