Favorable safety outcomes of a perioperative propranolol and etodolac regimen in cancer patients in four randomized controlled trials
Year: 2026
Type: article
Abstract: Background: The perioperative use of the β-adrenergic blocker, propranolol, and/or the semi-selective COX-2 inhibitor, etodolac, has improved biomarkers of cancer metastasis in several small randomized controlled trials (RCTs). In colorectal cancer (CRC) patients, the combined regimen showed potential to improve disease-free survival (DFS). Methods: We report data from our four RCTs including 148 patients with breast (n = 38), colorectal (n = 34 & n = 46), and pancreatic (n = 30) cancers. Treatment began 5 days pre-operatively, and continued for 5-30 postoperatively. Propranolol (slow-release) was initiated at 20 mg twice daily (b.i.d), increased to 80 mg b.i.d on surgery day, and gradually decreased thereafter to 20 mg b.i.d. Etodolac was provided at 400 mg b.i.d. The primary endpoints were perioperative safety outcomes, including adverse events (AEs) up to 30-day postoperatively, and 16 blood indices. Secondary outcomes were long-term oncological outcomes of 8-year DFS and overall survival (OS). Results: Bradycardia occurred in 12% of treated vs. 3% of placebo patients (p = 0.057), and was easily resolved by temporary withholding β-blockade. Weakness, nausea, pain, infection, bleeding, leakage, tissue-healing, or death were not significantly affected. Drug treatment promoted eosinophils in pancreatic cancer patients (p = 0.015), increased potassium (p = 0.013), and decreased albumin (p = 0.016) in CRC patients; however, these effects did not remain significant after false discovery rate (FDR) correction. In CRC, treatment improved 8-year DFS (2/15 vs. 9/18, p = 0.034), although this exploratory analysis was underpowered. Conclusion: These findings suggest the safety of this inexpensive and easy-to-implement perioperative propranolol and etodolac regimen in patients participating in these RCTs. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT00502684, https://clinicaltrials.gov/study/NCT00888797, https://clinicaltrials.gov/study/NCT03919461, https://clinicaltrials.gov/study/NCT03838029, identifier NCT00502684, NCT00888797, NCT03919461, NCT03838029.
Source: Frontiers in Pharmacology
Authors: Nahida Sakis, Liat Sorski, Eden Asraf, Itay Ricon-Becker, Lee Shaashua, Rita Haldar, Bar Bruno Shvalbo, Maytal Shabat-Simon, Mordechai Gutman, Aviram Nissan, Ido Nachmany, Ilan Kent, Ron Pery, Niv Pencovich, Noam Shussman, Nir Wasserberg, Avraham Reshef, Elchanan Quint, Yifat Yosef Lishtzinsky, Hanoch Kashtan, Moshe Shabtai, Baruch Brenner, Eran Sharon, Tanir Allweis, Nitzan Shahar, Anabel Eckerling, Elad Sandbank, Oded Zmora, Shamgar Ben-Eliyahu
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7155014654