Intraoperative ketorolac in high-risk breast cancer patients. A prospective, randomized, placebo-controlled clinical trial

Abstract

BackgroundKetorolac has been associated with a lower risk of recurrence in retrospective studies, especially in patients with positive inflammatory markers. It is still unknown whether a single dose of pre-incisional ketorolac can prolong recurrence-free survival.MethodsThe KBC trial is a multicenter, placebo-controlled, randomized phase III trial in high-risk breast cancer patients powered for 33% reduction in recurrence rate (from 60 to 40%). Patients received one dose of ketorolac tromethamine or a placebo before surgery. Eligible patients were breast cancer patients, planned for curative surgery, and with a Neutrophil-to-Lymphocyte Ratio≥4, node-positive disease or a triple-negative phenotype. The primary endpoint was Disease-Free Survival (DFS) at two years. Secondary endpoints included safety, pain assessment and overall survival.FindingsBetween February 2013 and July 2015, 203 patients were assigned to ketorolac (n = 96) or placebo (n = 107). Baseline characteristics were similar between arms. Patients had a mean age of 55.7 (SD14) years.At two years, 83.1% of the patients were alive and disease free in the ketorolac vs. 89.7% in the placebo arm (HR: 1.23; 95%CI: 0.65–2.31) and, respectively, 96.8% vs. 98.1% were alive (HR: 1.09; 95%CI: 0.34–3.51).ConclusionsA single administration of 30 mg of ketorolac tromethamine before surgery does not increase disease-free survival in high risk breast cancer patients. Overall survival difference between ketorolac tromethamine group and placebo group was not statistically significant. The study was however underpowered because of lower recurrence rates than initially anticipated. No safety concerns were observed.Trial registrationClinicalTrials.gov NCT01806259.

How Anesthetic, Analgesic and Other Non-Surgical Techniques During Cancer Surgery Might Affect Postoperative Oncologic Outcomes: A Summary of Current State of Evidence

“…Not only does it help the patient to recover faster from surgical trauma, but also decreases the number and severity of postoperative complications [75]. Non-complicated postoperative outcomes enable timely administration of oncological treatment as well as reduce the risk of applying suboptimal radio- and chemotherapy doses, which happen in nutritionally compromised patients [76]. It has also been shown that patients who suffer from postoperative complications have worse overall disease-free survival [77].…”

Breast cancer and the black swan

“…A recent, modest sized, randomised controlled trial, testing a single administration of 30 mg of ketorolac, versus placebo, in patients undergoing breast cancer surgery apparently did not confirm retrospective findings [94]. Besides a possible under-powering and quite short follow-up of the trial, patients were randomised according to a not soundly standardised factor, which could have introduced confounding unbalance between the trial arms of the frequency of usual prognostic factors (e.g., TNBC, treatment modalities, BMI etc.).…”

“…We propose that exploring the perioperative window will be a good place to start this process [80,81]. Other relevant papers have been published [82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99].…”

MAGI1, a Scaffold Protein with Tumor Suppressive and Vascular Functions

“…The biological effects of NSAIDs could be particularly relevant to the perioperative period, marked by an activation of inflammatory pathways [147]. Animal models and retrospective studies showed that perioperative administration of NSAIDs has been associated with lower risk of cancer recurrence [148,149]; however, other studies do not support their use [150,151]. Regular use of NSAIDs or COXIBs were also described to reduce the risk of other cancers, such as lung, esophageal, or CRC [152].…”