福沙匹坦预防儿童肿瘤患者高致吐化疗药物相关恶心呕吐有效性和安全性评估

doi:10.12372/jcp.2023.22e0483

摘要/Abstract

摘要：

目的探讨儿童肿瘤患者使用神经激肽1受体拮抗剂（NK-1RA）福沙匹坦预防高致吐性化疗（HEC）所致恶心呕吐（CINV）的临床疗效，并进行安全性评估。方法选择2021年7月至11月确诊恶性肿瘤并接受HEC治疗的患儿。将使用福沙匹坦+昂丹司琼+地塞米松预防HEC所致呕吐的患儿纳入福沙匹坦组，仅使用昂丹司琼+地塞米松治疗的患儿纳入对照组，比较两组治疗后的疗效和安全性。结果最终入组107例患儿，男51例、女56例，中位年龄3.5（1.4~7.3）岁。其中福沙匹坦组55例，对照组52例。福沙匹坦组和对照组之间整体、急性、延迟性呕吐阶段CINV程度分布差异均有统计学意义（P<0.05）。整体、急性、延迟性呕吐阶段福沙匹坦组的完全控制率（CCR）较高，轻/中度呕吐患儿比例较低，无重度呕吐患儿。福沙匹坦组25例（45.5%）发生不良反应，发生率低于对照组（34例，65.4%），差异有统计学意义（P<0.05）；两组患儿均未出现严重不良事件。两组患儿头痛、厌食、乏力等不良反应发生率差异均无统计学意义（P>0.05）。结论福沙匹坦联合昂丹司琼+地塞米松预防肿瘤患儿HEC相关恶心呕吐具有良好有效性和安全性。

关键词: NK-1受体拮抗剂, 福沙匹坦, 高致吐化疗药物, 安全性, 有效性

Abstract:

Objective To investigate the clinical efficacy and safety of fosaprepitant in preventing nausea and vomiting caused by highly emetogenic chemotherapy (HEC) in children with cancer. Methods Pediatric cancer patients who received fosaprepitant to manage HEC-induced nausea and vomiting in the Department of Hematology and Oncology of Shanghai Children's Medical Center between July 2021 and November 2021 were enrolled into this study. The patients treated with fosaprepitant+ondansetron+dexamethasone were included in the fosaprepitant group, and the patients treated with ondansetron+dexamethasone were included in the control group. The clinical efficacy was evaluated by the difference of complete response (CCR, no vomiting/rescue medication) of acute, delayed and overall phase vomiting between the two groups. The safety assessment was carried out using the Common Terminology Criteria for Adverse Events v4.0 (National Cancer Institute). Results 107 patients were enrolled in this study (55 in the fosaprepitant group and 52 in the control group). There were 51 males and 56 females, with a median age of 3.5 (1.42-7.33) years. CCR rates were higher in the fosaprepitant group comparing that in the control group during the acute, delayed vomiting and overall phases, a lower proportion of children with mild and moderate vomiting, and no children with severe vomiting. Adverse reactions occurred in 25 cases (45.5%) in the fosaprepitant group, with a lower incidence rate than that in the control group (34 cases, 65.4%), and the difference was statistically significant (P<0.05). No severe adverse event was observed in this study. The difference in the incidence of headache, anorexia, malaise and other adverse reactions between the two groups of children was not statistically significant (P>0.05). Conclusion Fosaprepitant combined with ondansetron and dexamethasone is effective and safe in preventing related nausea and vomiting in children with cancer.

Key words: NK-1 receptor antagonist, fosaprepitant, highly emetogenic chemotherapy drugs, security, effectiveness

于丽婷, 沈星伟, 王卓, 张顺国, 高怡瑾. 福沙匹坦预防儿童肿瘤患者高致吐化疗药物相关恶心呕吐有效性和安全性评估[J]. 临床儿科杂志, 2023, 41(8): 604-609.

YU Liting, SHEN Xingwei, WANG Zhuo, ZHANG Shunguo, GAO Yijin. Efficacy and safety of fosaprepitant in the prevention of highly emetogenic chemotherapy-related nausea and vomiting in pediatric patients with cancer[J]. Journal of Clinical Pediatrics, 2023, 41(8): 604-609.

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参考文献 23

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项目	福沙匹坦组(n=55)	对照组(n=52)	统计量	P
年龄[M(P₂₅~P₇₅)]/岁	3.3(1.4~4.9)	3.8(1.8~7.8)	Z =1.09	0.278
男性[n(%)]	30(54.5)	21(40.4)	χ²=2.15	0.143
体重[M(P₂₅~P₇₅)]/kg	13.3(10.7~18.2)	15.3(11.4~21.2)	Z =0.33	0.739
接受过化疗[n(%)]	46(83.6)	44(84.6)	χ²=0.02	0.896
诊断[n(%)]			-	0.509¹⁾
神经母细胞瘤	16(29.1)	10(19.2)
肝母细胞瘤	10(18.2)	7(13.5)
髓母细胞瘤	4(7.3)	1(1.9)
横纹肌肉瘤	11(20.0)	12(23.1)
尤文氏肉瘤	5(9.1)	9(17.3)
肾上腺皮质癌	2(3.6)	0(0.0)
淋巴母细胞瘤	3(5.5)	5(9.6)
生殖细胞瘤	1(1.8)	2(3.9)
肾母细胞瘤	0(0.0)	1(1.9)
肺母细胞瘤	3(5.5)	4(7.7)
急性淋巴细胞性白血病	0(0.0)	1(1.9)

呕吐类型	福沙匹坦组(n=55)	对照组(n=52)	Z值	P
急性呕吐
无呕吐(CR)	53(96.4)	37(71.2)	12.70	<0.001
轻度	2(3.6)	12(23.1 )
中度	0(0.0)	3(5.8)
严重	0(0.0)	0(0.0)
延迟性呕吐
无呕吐(CR)	44(80.0)	32(61.5)	4.42	0.035
轻度	10(18.2)	14(26.9)
中度	1(1.8)	4(7.7)
严重	0(0.0)	2(3.8)
整体呕吐
无呕吐(CR)	42(76.4)	17(32.7)	20.60	<0.001
轻度	12(21.8)	26(50.0)
中度	1(1.8)	7(13.5)
严重	0(0.0)	2(3.9)

不良反应	福沙匹坦组(n=55)	对照组(n=52)	χ²值	P
头晕	1(1.8)	1(1.9)	-	1.000¹⁾
发热	2(3.6)	6(11.5)	-	0.154¹⁾
厌食	21(38.2)	15(28.8)	1.04	0.307
腹部不适	1(1.8)	2(3.8)	-	0.611¹⁾
咳嗽	4(7.3)	5(9.6)	-	0.737¹⁾
腹泻	4(7.3)	2(3.8)	-	0.679¹⁾
便秘	5(9.1)	5(9.6)	-	1.000¹⁾
中性粒细胞减少1、2级	18(32.7)	18(34.6)	0.04	0.836
中性粒细胞减少3、4级	5(9.1)	7(13.5)	0.51	0.474
WBC减少1、2级	23(41.8)	24(46.2)	0.41	0.520
WBC减少3、4级	8(14.5)	10(19.2)	0.20	0.652
血小板减少	1(1.8)	4(7.7)	-	0.197¹⁾
乏力	6(10.9)	2(3.8)	-	0.272¹⁾
恶心	3(5.5)	10(19.2)	3.55	0.067
牙痛	1(1.8)	0(0.0)	-	1.000¹⁾
喉咙痛	1(1.8)	0(0.0)	-	1.000¹⁾
烦躁	1(1.8)	0(0.0)	-	1.000¹⁾