A Comparison of Fentanyl and Flurbiprofen Axetil on Serum VEGF-C, TNF-α, and IL-1ß Concentrations in Women Undergoing Surgery for Breast Cancer

Pain Pract. 2015 Jul;15(6):530-7. doi: 10.1111/papr.12206. Epub 2014 May 8.

Abstract

Background: Vascular endothelial growth factor-C (VEGF-C), tumor necrosis factor-α (TNF-α), and interleukin-1ß(IL-1ß) have been shown to be associated with the recurrence and metastasis of breast cancer after surgery. This study tested the hypothesis that patients undergoing surgery for breast cancer, who received postoperative analgesia with flurbiprofen axetil combined with small doses of fentanyl (FA), exhibited reduced levels of VEGF-C, TNF-α, and IL-1ß compared with those patients receiving fentanyl alone (F).

Method: Forty-women with primary breast cancer undergoing a modified radical mastectomy were randomized to receive postoperative analgesia with flurbiprofen axetil combined with fentanyl or fentanyl alone. Venous blood was sampled before anesthesia, at the end of surgery, and at 48 hours after surgery, and the serum was analyzed. The primary endpoint was changes in the VEGF-C concentrations in serum.

Results: Group FA patients reported similar analgesic effects as group F patients at 2, 24, and 48 hours. At 48 hours, mean postoperative concentrations of VEGF-C in group F patients were higher than in group FA patients, 730.9 versus. 354.1 pg/mL (P = 0.003), respectively. The mean postoperative concentrations of TNF-α in group F patients were also higher compared with group FA patients 27.1 vs. 15.8 pg/mL (P = 0.005). Finally, the mean postoperative concentrations of IL-1ß in group F were also significantly higher than in group FA 497.5 vs. 197.7 pg/mL (P = 0.001).

Conclusion: In patients undergoing a mastectomy, postoperative analgesia with flurbiprofen axetil, combined with fentanyl, were associated with decreases in serum concentrations of VEGF-C, TNF-α, and IL-1ß compared with patients receiving doses of only fentanyl.

Keywords: analgesia; immunologic factors; postoperative pain.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Analgesics / administration & dosage*
  • Breast Neoplasms / blood
  • Breast Neoplasms / surgery
  • Drug Therapy, Combination / methods
  • Female
  • Fentanyl / administration & dosage*
  • Flurbiprofen / administration & dosage
  • Flurbiprofen / analogs & derivatives*
  • Humans
  • Interleukin-1beta / blood*
  • Interleukin-1beta / drug effects
  • Middle Aged
  • Pain, Postoperative / prevention & control
  • Tumor Necrosis Factor-alpha / blood*
  • Tumor Necrosis Factor-alpha / drug effects
  • Vascular Endothelial Growth Factor C / blood*
  • Vascular Endothelial Growth Factor C / drug effects

Substances

  • Analgesics
  • Interleukin-1beta
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor C
  • Flurbiprofen
  • flurbiprofen axetil
  • Fentanyl