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Updated: May 23, 2025

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Pancreatic resection with perioperative drug repurposing of propranolol and etodolac - the phase II randomized

Felix J Hüttner1,2, Rosa Klotz1,3, Nathalia A Giese1

  • 1Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany.

Langenbeck'S Archives of Surgery
|May 22, 2025
PubMed
Summary

Perioperative drug repurposing with propranolol and etodolac showed no safety concerns in pancreatic cancer surgery. While recruitment was challenging, preliminary data suggest potential benefits in disease-free survival and reduced recurrence.

Keywords:
BetablockadeCOX-2-inhibitionInflammationPancreatic cancerPerioperative period

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Area of Science:

  • Oncology
  • Pharmacology
  • Surgical Oncology

Background:

  • Perioperative stress and inflammation can drive pancreatic cancer recurrence.
  • Catecholamines and prostaglandins are key mediators of these perioperative reactions.
  • Drug repurposing offers a strategy to mitigate these effects.

Purpose of the Study:

  • To assess the feasibility and safety of perioperative drug repurposing with propranolol (a non-selective betablocker) and etodolac (a COX-2 inhibitor) in pancreatic cancer surgery.
  • To evaluate the impact of this drug combination on disease recurrence and survival.

Main Methods:

  • Randomized trial of pancreatic cancer patients undergoing partial pancreatoduodenectomy.
  • Intervention group received perioperative propranolol and etodolac; control group received placebo.
  • Primary endpoints: safety (serious adverse events) and feasibility (adherence).
  • Secondary endpoints: overall survival, disease-free survival (DFS), and recurrence rates.

Main Results:

  • Trial closed early due to slow recruitment; 9 patients received treatment, 11 received placebo.
  • No significant safety concerns identified; fewer serious adverse events in the treatment group.
  • Median DFS was longer in the treatment group (16.36 months vs. 11.25 months).
  • Distant recurrence rate was significantly lower in the treatment group (11.1% vs. 54.5%).

Conclusions:

  • Perioperative drug repurposing with propranolol and etodolac was not feasible due to recruitment and adherence challenges.
  • Despite feasibility issues, preliminary efficacy data suggest potential benefits in DFS and reduced recurrence.
  • Further investigation is warranted based on promising translational and efficacy findings.