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.
The Anticancer Fund, Brussels, Belgium.
PLoS One. 2019 Dec 4;14(12):e0225748. doi: 10.1371/journal.pone.0225748. eCollection 2019.
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.
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.
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).
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.
ClinicalTrials.gov NCT01806259.
在回顾性研究中，酮咯酸与较低的复发风险相关，尤其是在炎症标志物阳性的患者中。目前尚不清楚单次术前使用酮咯酸能否延长无复发生存期。
KBC 试验是一项多中心、安慰剂对照、随机 III 期临床试验，旨在高危乳腺癌患者中降低 33%的复发率（从 60%降至 40%）。患者在手术前接受一次酮咯酸托品或安慰剂治疗。符合条件的患者为计划行根治性手术的乳腺癌患者，中性粒细胞与淋巴细胞比值≥4、淋巴结阳性疾病或三阴性表型。主要终点为两年时的无病生存（DFS）。次要终点包括安全性、疼痛评估和总生存。
2013 年 2 月至 2015 年 7 月，203 例患者被分配至酮咯酸组（n=96）或安慰剂组（n=107）。两组患者的基线特征相似。患者的平均年龄为 55.7（SD14）岁。两年时，酮咯酸组 83.1%的患者存活且无疾病，安慰剂组为 89.7%（HR：1.23；95%CI：0.65-2.31），相应地，96.8%的患者存活，安慰剂组为 98.1%（HR：1.09；95%CI：0.34-3.51）。
手术前单次给予 30mg 酮咯酸托品不能增加高危乳腺癌患者的无病生存率。酮咯酸托品组与安慰剂组的总生存差异无统计学意义。然而，由于复发率低于预期，该研究的效力不足。未观察到安全性问题。
ClinicalTrials.gov NCT01806259。
