Pancreatic cancer: early results of PROSPER-trial with repurposed medication show potential to improve outcomes
BRUSSELS - Researchers at Heidelberg University Hospital have completed the PROSPER trial, a clinical study examining whether two commonly available medications—propranolol and etodolac—could improve outcomes when administered around the time of pancreatic cancer surgery. The trial was funded by Anticancer Fund.
Pancreatic cancer remains one of the most aggressive forms of cancer, with a five-year survival rate among the lowest of all major cancers. The disease is often diagnosed at advanced stages, making treatment extremely difficult. Even when surgical removal of the tumour is possible, the majority of patients experience cancer recurrence.
Study design and implementation
The trial enrolled 20 patients undergoing pancreatic cancer surgery. Nine patients received propranolol (a beta-blocker used for hypertension) and etodolac (a non-steroidal anti-inflammatory drug) for 25 days: 10 days before surgery and 14 days after. Eleven patients received placebo treatment. All participants were monitored for a minimum of two years.
The study targeted the perioperative period, which is characterized by stress and inflammatory responses that may contribute to cancer recurrence and metastatic spread. This treatment window has not been systematically investigated in pancreatic cancer.
The trial was terminated early due to recruitment challenges. Many patients experienced difficulty swallowing medications due to digestive complications associated with pancreatic cancer, limiting enrolment below the originally planned target.
The main investigators of this trial were Prof. Dr. Med. Felix J. Hüttner And Prof. Dr. Markus K. Diener. The study was led by Prof. Dr. Med. Pascal Probst and Prof. Dr. Med. Phillip Knebel under the guidance of Prof. Dr. Markus W. Büchler at the University of Heidelberg’s surgery department.
Outcomes
The results should be seen as exploratory, because of the small patient cohort, but nevertheless the study documented relevant differences between groups:
Safety: No adverse events or safety concerns were observed with the drug combination compared to placebo.
Survival: Patients in the drug treatment group demonstrated longer median overall survival and disease-free survival as compared to the placebo group.
Metastases: 11% of patients receiving the drug combination developed distant metastases, compared to 54% in the placebo group.
Next steps
The PROSPER trial represents an investigation into drug repurposing, using medications developed for other medical conditions in cancer treatment. This approach aligns with Anticancer Fund's mission to bring new treatments to patients faster by innovating with existing drugs.
Future research will need to address the key challenges identified in the PROSPER trial, including feasibility issues for pancreatic cancer patients and difficulties with medication adherence during the postoperative period. A larger trial is essential to establish statistically robust and clinically meaningful benefits of this novel treatment.
Interview
Dr. Hüttner, what makes pancreatic cancer so challenging to treat?
Dr. Hüttner: "Pancreatic cancer is hard to treat due to several aspects: most cancers are discovered at an advanced stage; there are still limited systemic treatment options; and surgery is technically demanding for anatomical reasons. Thus, every therapeutic window needs to be exploited in order to achieve the best outcome for patients."
What was the approach behind the PROSPER trial?
Dr. Hüttner: "Within the PROSPER trial, we tried to use the timespan surrounding surgery – a period that is usually not yet exploited for a cancer-directed therapy, with two common non-oncology drugs. Although, we had some problems with the feasibility of the planned trial intervention and we had to terminate the trial early with less included patients than initially planned, the results showed some interesting and promising findings."
What were the key findings from the study?
Dr. Hüttner: "First of all, the drug treatment was safe without concerns about adverse events or other safety issues compared to placebo. Second, the survival outcomes as well as the rate of distant metastases showed some promising improvements for the treatment group. However, these latter results have to be interpreted with substantial caution, because of the low number of patients and thus the low power of the study."
How do these results fit into the broader cancer research landscape?
Dr. Hüttner: "There are similar findings from studies evaluating this drug treatment in other cancers, such as colorectal and breast cancer. This warrants further investigation of this concept in future research, in which the lessons learned from PROSPER should be considered to make the intervention more feasible in order to accrue more patients."
About Felix Hüttner
Dr. Felix Hüttner is a surgeon and clinical researcher based at Heidelberg University Hospital, one of Germany's most renown medical institutions and home to the European Pancreas Center.
Dr. Hüttner is particularly known for his innovative approach to clinical trials and his commitment to finding practical, accessible solutions for cancer patients. He is the main investigator of the PROSPER trial, a study representing a shift in thinking about cancer treatment – taking everyday medications and repurposing them as tools in the fight against pancreatic cancer.
Working within Heidelberg's world-class pancreatic surgery program, which performs over 700 pancreatic cancer operations annually, Dr. Hüttner combines surgical expertise with clinical research to improve outcomes for patients.