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Perioperative use of a β-blocker and an anti-inflammatory drug in pancreatic cancer

Pancreatic Resection with perioperative Off-label Study of Propranolol and Etodolac – a phase II Randomised trial (PROSPER).

Cancer types
Pancreatic cancer
Trial phase


ACF funding

Why this trial

As pancreatic cancers in general, also pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, has a very poor prognosis and rising incidence. Only 15 to 20 percent of PDAC have no sign of metastasis at diagnosis and are deemed operable. For patients with an operable tumour, upfront surgery is the standard of care followed by adjuvant chemotherapy. Nevertheless, the 5-year overall survival of these patients is approximately 20% and almost 50% relapses within the first year after surgery. Clearly, there is a need to reduce the number of relapses which will improve the overall survival of these patients.

Why this intervention

Research shows that the time period between diagnosis and surgery represents a window of opportunity for therapy aiming at reducing recurrence. Pancreatic disease recurrence appears to be stimulated by perioperative psychological and surgical stress. Psychological stress is mediated by catecholamines (noradrenalin and adrenalin) and beta-adrenergic signalling, while surgical stress is mediated by prostaglandins synthesised by cyclo-oxygenase 2 (COX2) enzymes, which are typically overexpressed in pancreatic tumour cells.

Many studies indicate that the mechanisms of catecholamines and prostaglandins play an important role in the progression of PDAC, PDAC cell invasion and proliferation, and tumour metastasis. Perioperative co-administration of the beta-blocker propranolol and the COX2-inhibitor etodolac in patients with locally advanced or metastatic pancreatic cancer, showed that overall survival increased with 7 months.

Therefore, the perioperative co-administration of propranolol and etodolac may also contribute to reducing recurrence of newly diagnosed resectable PDAC.

Trial design

This was a phase II, randomised, two-armed, double-blinded, placebo-controlled, single-centre trial of a combination therapy of propranolol and etodolac in 100 patients with operable cancer of the pancreatic head planned for elective pancreatoduodenectomy.

The primary objective was to study the safety, feasibility and generate first efficacy data of perioperative propranolol and etodolac in these patients. Eligible patients were randomised between a daily intake of placebo from 10 days before surgery to 14 days after surgery, or daily intake of 2 doses of 400mg etodolac from 10 days before surgery to 14 days after surgery and 2 doses of 20mg propranolol daily during the 10 days before the surgery, 2 doses of 40mg propranolol on the day of surgery and one week after, and 2 doses of 20mg propranolol the second week after the operation. The total duration of treatment was 25 days and the follow-up was 24 months.



Results are expected in Q2 2024.


Principal Investigators:

  • Prof. Dr. Med. Pascal Probst, Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
  • Prof. Dr. Med. Phillip Knebel (deputy PI), Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany


  • Ruprecht-Karls-University, Heidelberg Medical Faculty, Universitätsklinikum Heidelberg, Heidelberg, Germany

Our role

Financial support
Scientific / Strategic input

Why we support this trial

Intervention has little or no commercial value

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Expected survival benefit

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No major hurdle for clinical implementation

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ACF funding

Questions about participation?

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Questions about this trial?

The Anticancer Fund
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Kim-Fuchs, C., et al. (2014). Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment. Brain, Behavior, and Immunity, 40, 40-7. doi:10.1016/j.bbi.2014.02.019

Partecke, L.I., et al. (2016). Chronic stress increases experimental pancreatic cancer growth, reduces survival and can be antagonised by beta-adrenergic receptor blockade. Pancreatology, 16(3), 423-33. doi:10.1016/j.pan.2016.03.005

Siegel, R.L., et al. (2015). Cancer statistics, 2015. CA Cancer J Clin, 65(1),5-29. doi:10.3322/caac.21254

Valle, J. W., et al. (2014). Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: Ongoing lessons from the ESPAC-3 study. J. Clin. Oncol., 32(6),504-12. doi:10.1200/JCO.2013.50.7657

Hüttner, F. J., et al (2020). Pancreatic resection with perioperative drug repurposing of propranolol and etodolac: trial protocol of the phase-II randomised placebo controlled PROSPER trial. BMJ Journals, 2020 Sep 30;10(9):e040406, doi: 10.1136/bmjopen-2020-040406.

Author: Kristine Beckers (Trial Manager)

Last updated: March 2024.