Perioperative propranolol (β-blocker) + etodolac (COX-2 inhibitor) shows manageable bradycardia and exploratory DFS signal in CRC

Perioperative propranolol (non-selective β-adrenergic blocker; slow-release, titrated from 20mg BID pre-op to 80mg BID on surgery day) plus etodolac (semi-selective COX-2 inhibitor; 400mg BID) was evaluated across four placebo-controlled RCTs in resectable breast (n=38), colorectal (n=34 and n=46), and pancreatic (n=30) cancers (total n=148; NCT00502684, NCT00888797, NCT03919461, NCT03838029). The primary endpoint was 30-day perioperative safety (AEs and 16 blood indices): bradycardia was higher with treatment (12% vs 3%; p=0.057) but reportedly resolved with temporary β-blocker holds; no significant differences were seen in weakness, nausea, pain, infection, bleeding, leakage, tissue-healing, or death, and several lab shifts did not remain significant after FDR correction. In an underpowered, exploratory CRC subset with long-term follow-up, 8-year DFS events were 2/15 on treatment vs 9/18 on placebo (p=0.034); for context, modern curatively resected stage II–III colon cancer typically sees ~75% 3-year DFS with standard adjuvant fluoropyrimidine/oxaliplatin regimens, so any durable DFS separation would need confirmation in larger, adequately staged cohorts.