| 摘要: |
| 目的 比较神经激肽 1(NK-1)受体拮抗剂(RA)联合托烷司琼与地塞米松联合托烷司琼预防中度致吐风险化疗所致恶心呕吐(MEC-CINV)的效果。方法 采用非劣效性试验设计,将中国人民解放军南部战区总医院肿瘤科 2021 年 4 月至 2022 年 1 月满足条件的拟接受中度致吐风险化疗的肿瘤患者按照随机数字表法分为 NK-1RA 组和地塞米松组。NK-1 RA 组患者采用 NK-1 RA(阿瑞匹坦或福沙匹坦) +托烷司琼二联止吐方案,地塞米松组采用托烷司琼+地塞米松标准二联止吐方案。主要评价指标为总观察期(0~120 h)、延迟期(24~120 h)、急性期(24 h 内)的呕吐完全缓解(CR)率,次要评价指标为各期恶心完全控制(CC)率及恶心呕吐总缓解(TR)率,安全性指标为止吐药物的不良反应(包括乏力、便秘、呃逆、失眠等症状指标,以及白细胞计数减少、中性粒细胞计数减少、血红蛋白下降、血小板计数减少、丙氨酸转氨酶和/或天冬氨酸转氨酶升高、血肌酐升高等实验室指标异常)。采用差异性检验(检验水准为 0.05)和非劣效性检验(非劣效性界值为 15 %,检验水准为 0.025)比较两组的干预效果。结果 最终共有 101 例患者全程参与本研究,其中 NK-1 RA 组 51 例,地塞米松组 50 例。NK-1RA 组和地塞米松组总观察期呕吐 CR 率分别为 58.8 %(30/51)和 56.0 %(28/50),非劣效性检验无统计学意义[P非劣效=0.035,率差(RD)=2.80 %, 95 % CI -16.5 %~22.1 %];急性期呕吐 CR 率分别为 80.4 %(41/51)和78.0 %(39/50),非劣效性检验有统计学意义(P非劣效=0.016, RD=2.40 %, 95 % CI -13.4 %~18.2 %);延迟期呕吐CR 率分别为 62.7 %(32/51)和 58.0 %(29/50),非劣效性检验有统计学意义(P非劣效=0.021, RD=4.70 %, 95 % CI-14.4 %~23.8 %)。NK-1 RA 组各期恶心 CC 率略高于地塞米松组,非劣效性检验有统计学意义(均 P非劣效<0.025)。两组间各安全性指标差异无统计学意义(均 P>0.05)。结论 在 MEC-CINV 患者中, NK-1 RA 联合托烷司琼的二联止吐方案对恶心呕吐的控制效果非劣效于地塞米松联合托烷司琼标准二联止吐方案,且安全性良好。 |
| 关键词: 中度致吐风险化疗 恶心 呕吐 5-羟色胺3受体拮抗剂 神经激肽1受体拮抗剂 地塞米松 |
| DOI：10.16781/j.CN31-2187/R.20240081 |
| 投稿时间：2024-01-29修订日期：2024-03-29 |
| 基金项目:广州市科技计划项目(201804010222). |
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| Neurokinin-1 receptor antagonist as an alternative to dexamethasone in standard dual regimen for moderately emetogenic chemotherapy-induced nausea and vomiting: a randomized controlled trial |
| NIE Wuyi1,ZHOU Juan2,CHENG Donghai2,WANG Haoqiang2,XIE Bo2* |
(1. Graduate School, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, China;
2. Department of Oncology, General Hospital of Southern Theater Command of PLA, Guangzhou 510006, Guangdong, China
*Corresponding author) |
| Abstract: |
| Objective To compare the effects of neurokinin-1 (NK-1) receptor antagonist (RA) plus tropisetron versus dexamethasone plus tropisetron against moderately emetogenic chemotherapy-induced nausea and vomiting (MECCINV). Methods A non-inferiority trial was designed. Patients who received moderately emetogenic chemotherapy in Department of Oncology of General Hospital of Southern Theater Command of PLA from Apr. 2021 to Jan. 2022 were randomly assigned to NK-1 RA (NK-1 RA+tropisetron) group or dexamethasone (tropisetron+dexamethasone) group by random number table method. Primary evaluation indexes were complete response (CR) rates of vomiting at overall phase (0- 120 h), delayed phase (24-120 h) and acute phase (<24 h). Secondary evaluation indexes were complete control (CC) rate of nausea and total response (TR) rate of nausea and vomiting at each phase. Safety indexes were adverse events (symptoms such as fatigue, constipation, hiccup and insomnia; abnormal laboratory indicators such as decline of leukocyte, neutrophil, hemoglobin and platelet and increase of alanine transaminase and/or aspartate transaminase and serum creatinine). The intervention effects of the 2 groups were compared by difference test (test level was 0.05) and non-inferiority test (noninferiority margin was 15 %, and test level was 0.025). Results A total of 101 patients participated in the study, including 51 in the NK-1 RA group and 50 in the dexamethasone group. The CR rates of vomiting at overall phase in the NK-1 RA group and dexamethasone group were 58.8 % (30/51) and 56.0 % (28/50), respectively, and non-inferiority test showed no statistical significance (Pnon-inferiority=0.035, rate difference[RD]=2.80 %, 95 % confidence interval[CI]-16.5 %-22.1 %); the CR rates of vomiting at acute phase were 80.4 % (41/51) and 78.0 % (39/50), respectively, and non-inferiority test was statistically significant (Pnon-inferiority=0.016, RD=2.40 %, 95 % CI -13.4 %-18.2 %); and the CR rates of vomiting at delayed phase were 62.7 % (32/51) and 58.0 % (29/50), respectively, and non-inferiority test was statistically significant (Pnon-inferiority=0.021, RD=4.70 %, 95 % CI -14.4 %-23.8 %). The CC rate of nausea at each phase was slightly higher in the NK-1 RA group than that in the dexamethasone group, and the non-inferiority test was statistically significant (all Pnon-inferiority<0.025). There was no significant difference in the safety indicators between the 2 groups (all P>0.05). Conclusion In MEC-CINV patients, the control effect of antiemetic regimen of NK-1 RA combined with tropisetron on nausea and vomiting is non-inferior to the standard dual regimen dexamethasone combined with tropisetron, and the safety is good. |
| Key words: moderately emetogenic chemotherapy nausea vomiting 5-hydroxytryptamine 3 receptor antagonist neurokinin-1 receptor antagonist dexamethasone |
