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Effect of perioperative COX-2 and beta-adrenergic inhibition on 5-year disease-free-survival in colorectal cancer: A pilot randomized controlled Colorectal Metastasis PreventIon Trial (COMPIT)

Published:October 20, 2022DOI:https://doi.org/10.1016/j.ejso.2022.10.013

      Abstract

      Introduction

      Based on translational and epidemiological evidence, perioperative inhibition of beta-adrenergic and COX2 signaling can reduce the risk for post-surgical metastatic disease. Here we aimed to assess in a pilot study the impact of a perioperative combined COX-2 and beta-adrenergic blockade on long-term cancer outcomes in colorectal cancer patients undergoing curative surgery.

      Materials and methods

      Thirty-four newly diagnosed colorectal cancer patients without evidence of metastases enrolled in this double-blinded placebo-controlled randomized clinical trial (treatment, n = 16; placebo, n = 18). A 20-day oral treatment of propranolol and etodolac regimen was initiated 5 days before surgery. Beneficial effects on short-term molecular biomarkers of cancer progression were reported earlier. Here we present outcomes of five postoperative years of disease-free-survival and overall survival.

      Results

      Adverse event rates were equivalent between the two groups. Intent-to-treat analyses of 5-year follow-up showed that 2/16 (12.5%) vs 9/18 (50%) patients exhibited recurrence in treatment vs placebo groups, respectively (p = 0.033), and 2/16 (12.5%) vs 4/18 (22%) died (p = 0.467). In protocol compliant patients 0/11 (0%) vs. 8/17 (47%) exhibited recurrence in treatment vs. placebo groups, respectively (p = 0.007), and 0/11 (0%) and 3/17 (17.6%) died (p = 0.151).

      Conclusions

      In this pilot clinical trial, a combined perioperative treatment with propranolol and etodolac significantly improved 5-year disease-free-survival. The small sample size and a single center study design merits caution in interpreting these results, specifically in estimating the effect-size. Larger studies in colorectal cancer are warranted and needed.

      Keywords

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