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


Autoři: Patrice Forget aff001;  Gauthier Bouche aff002;  Francois P. Duhoux aff003;  Pierre G. Coulie aff004;  Jan Decloedt aff005;  Alain Dekleermaker aff006;  Jean-Edouard Guillaume aff007;  Marc Ledent aff008;  Jean-Pascal Machiels aff003;  Véronique Mustin aff008;  Walter Swinnen aff009;  Aline van Maanen aff010;  Lionel Vander Essen aff008;  Jean-Christophe Verougstraete aff011;  Marc De Kock aff012;  Martine Berliere aff013
Působiště autorů: Institute of Applied Health Sciences, Epidemiology group, School of Medicine, Medical Science and Nutrition, University of Aberdeen, Department of Anaesthesia, NHS Grampian, Aberdeen, United Kingdom aff001;  The Anticancer Fund, Brussels, Belgium aff002;  Institut Roi Albert II, Service d’Oncologie Médicale, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (POLE MIRO), UCLouvain, Brussels, Belgium aff003;  de Duve Institute, UCLouvain, Brussels, Belgium aff004;  Department of Oncology, St-Blasius Hospital, Dendermonde, Belgium aff005;  Clinical Pharmacology Unit, Cliniques Universitaires Saint-Luc, Brussels, Belgium aff006;  Department of Anesthesiology, Ste-Elisabeth hospital, Namur, Belgium aff007;  Department of Anesthesiology, St-Pierre Clinic, Ottignies, Belgium aff008;  Department of Anesthesiology, St-Blasius Hospital, Dendermonde, Belgium aff009;  Biostatistics Unit, King Albert II Institute, Cliniques Universitaires Saint-Luc, Brussels, Belgium aff010;  Department of Gynecology, St-Pierre Clinic, Ottignies, Belgium aff011;  Department of Anesthesiology, Centre Hospitalier Wallonie Picarde (CHWAPI), Tournai, Belgium aff012;  Department of Gynecology, Breast Clinic, King Albert II Institute, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium aff013
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225748

Souhrn

Background

Ketorolac 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.

Methods

The 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.

Findings

Between 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).

Conclusions

A 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 registration

ClinicalTrials.gov NCT01806259.

Klíčová slova:

Adverse events – Breast cancer – Cancer treatment – NSAIDs – Retrospective studies – Surgical and invasive medical procedures – Surgical oncology


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