# Perioperative beta-blocker plus COX-2 inhibitor to reduce metastasis after surgery

Source: https://onco.cc/ideas/idea-reg-perioperative-propranolol-etodolac/  
OnCo record `idea-reg-perioperative-propranolol-etodolac` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Surgical stress releases catecholamines and prostaglandins that suppress anti-tumour immunity and help metastatic cells seed. Phase 2 trials of a five-day course of propranolol plus etodolac around breast and colorectal surgery shifted tumour markers of metastasis and immune suppression in the right direction; both drugs cost cents, and a publicly funded phase 3 is the missing step.

## Summary

Surgical stress releases catecholamines and prostaglandins that suppress anti-tumour immunity and promote metastatic seeding in animal models. Phase 2 trials of propranolol plus etodolac around surgery in breast and colorectal cancer (Ben-Eliyahu and colleagues) showed favourable changes in tumour transcriptomic markers of metastasis and immune suppression, and a small colorectal trial suggested reduced recurrence. Both drugs cost cents. The proposal is a publicly funded, multinational phase 3 in colorectal and breast cancer with disease-free survival as the primary endpoint.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Perioperative propranolol and etodolac for about five days improve 5-year disease-free survival by an absolute 5 percentage points or more in stage II-III colorectal cancer compared with placebo.
- Rationale: The biology is well characterised, the intervention is short, and the perioperative window is a plausible point of vulnerability for micrometastatic disease that no expensive therapy targets.
- Proposed test: Phase 3 randomised placebo-controlled trial of roughly 1,500 patients in colorectal cancer with DFS primary endpoint and recurrence transcriptomic biomarkers in a sub-study.
- Maturity: early-clinical
- Actor: research

## Sources

- Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014): https://doi.org/10.3332/ecancer.2014.442

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/)
- bottlenecks: [Metastasis is understood least and studied last](https://onco.cc/bottlenecks/b-metastasis-biology/), [No incentive to repurpose cheap drugs](https://onco.cc/bottlenecks/b-generic-repurposing/)
- key papers: [The Repurposing Drugs in Oncology (ReDO) Project](https://onco.cc/key-papers/paper-pantziarka-ecancermedicalscience/)

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