Abstract # 1733 The perioperative use of a beta-adrenergic blocker and a COX-2 inhibitor in colorectal cancer patients for the prevention of cancer recurrence: A preliminary study assessing feasibility and safety

Abstract

Translational studies, including our studies in various tumor models, indicate that excess perioperative release of catecholamines and prostaglandins synergistically mediate surgery-induced promotion of cancer metastasis. Here we assessed the clinical feasibility and safety of the combined perioperative use of the beta-adrenergic blocker, propranolol, and the COX-2 inhibitor, etodolac. A double-blind placebo-controlled clinical trial was conducted in non-metastatic colorectal cancer patients undergoing curative resection (2010-2015, Sheba Medical Center, Israel). Of the diagnosed patients, ∼60% were excluded, mainly due to asthma, diabetes, or chronic use of similar medications, and ∼50% of eligible patients agreed to participate. A continuous 20-day oral drug treatment was initiated five days before surgery; perioperative drug-related and overall complication rates were studied; and a three-year follow-up for cancer recurrence is ongoing. Of the 15 patients randomly allocated to drug treatment, two (13%) were excluded due to low compliance, one due to bradycardia (6.7%); and two more (13%) had tolerable bradycardia levels. Of the 20 placebo patients, one suffered breathing difficulties (5%). No other medication-related complications were recorded. One patient per group exhibited metastases during surgery (excluded). A total of 15 post-operative adverse events (in 11 categories) occurred, with no overall difference between the groups (p = 0.3). Cancer recurrence occurred in 4 placebo patients (21%) and 1 drug-treated patient (8%) (p = 0.35). Overall, the herein perioperative use of propranolol and etodolac is feasible and apparently safe.