Intraoperative ketorolac in high-risk breast cancer patients. A prospective, randomized, placebo-controlled clinical trial
Intraoperative ketorolac in high-risk breast cancer patients. A prospective, randomized, placebo-controlled clinical trial
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DOI：
10.1371/journal.pone.0225748
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发表时间：
2019-12-04
期刊：
影响因子：
3.7
通讯作者：
Berliere, Martine
中科院分区：
文献类型：
--
作者：
Forget, Patrice;Bouche, Gauthier;Berliere, Martine
背景回顾性研究发现，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。它仍然是未知的，是否单剂量的切口前酮咯酸可以延长复发无survival.MethodsThe KBC试验是一个多中心，安慰剂对照，随机III期临床试验中的高危乳腺癌患者的权力为33%的复发率降低（从60至40%）。患者在手术前接受一剂酮咯酸氨丁三醇或安慰剂。符合条件的患者是计划进行根治性手术的乳腺癌患者，中性粒细胞与淋巴细胞比率>= 4，淋巴结阳性疾病或三阴性表型。主要终点是2年时的无病生存期（DFS）。次要终点包括安全性、疼痛评估和总生存率。结果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）。两组的基线特征相似。患者的平均年龄为55.7岁（SD 14），2年时，酮咯酸组83.1%的患者存活且无疾病，而安慰剂组为89.7（HR：1.23; 95%CI：0.65-2.31）和分别为96.8%和98.1%的患者存活（HR：1.09; 95%CI：结论术前单次给予30 mg酮咯酸氨丁三醇不会增加疾病发生率，高危乳腺癌患者的自由生存。酮咯酸氨丁三醇组和安慰剂组的总生存期差异无统计学意义。然而，由于复发率低于最初预期，该研究的效力不足。未观察到安全性问题。
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.