{"entity":{"id":"idea-reg-perioperative-propranolol-etodolac","kind":"idea","name":"Perioperative beta-blocker plus COX-2 inhibitor to reduce metastasis after surgery","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":["colorectal","breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-metastasis-biology"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"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.","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","cost":"medium","horizonYears":6},"route":"/ideas/idea-reg-perioperative-propranolol-etodolac/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"}],"bottleneck":[{"id":"b-metastasis-biology","kind":"bottleneck","name":"Metastasis is understood least and studied last","route":"/bottlenecks/b-metastasis-biology/"},{"id":"b-generic-repurposing","kind":"bottleneck","name":"No incentive to repurpose cheap drugs","route":"/bottlenecks/b-generic-repurposing/"}],"paper":[{"id":"paper-pantziarka-ecancermedicalscience","kind":"paper","name":"The Repurposing Drugs in Oncology (ReDO) Project","route":"/key-papers/paper-pantziarka-ecancermedicalscience/"}]}}