华蟾素治疗肝癌肝动脉灌注化疗术后疼痛的疗效和安全性

doi:10.3877/cma.j.issn.2095-3232.2025.04.011

中华肝脏外科手术学电子杂志 ›› 2025, Vol. 14 ›› Issue (04) : 569 -575. doi: 10.3877/cma.j.issn.2095-3232.2025.04.011

临床研究

华蟾素治疗肝癌肝动脉灌注化疗术后疼痛的疗效和安全性

吴添庆¹^,², 郑梽楷¹^,², 贺珉睿¹^,², 潘扬勋¹^,², 王骏成¹^,², 陈锦滨¹^,², 周仲国¹^,²^,^†(

)

¹510060　广州，华南恶性肿瘤防治全国重点实验室　广东省恶性肿瘤临床医学研究中心　中山大学肿瘤防治中心
²510060　广州，中山大学肿瘤防治中心肝脏外科

收稿日期:2025-02-12 出版日期:2025-08-10
通信作者: 周仲国
基金资助:
国家自然科学基金(82303893); 广东省自然科学基金(2024A1515012966); 吴阶平医学基金会临床科研专项资助基金(320.6705.2021-02-76); 中山大学肿瘤防治中心临床医学科学家基金(16zxqk04)

Efficacy and safety of cinobufotalin in treatment of pain after hepatic arterial infusion chemotherapy for primary liver cancer

Tianqing Wu¹^,², Zhikai Zheng¹^,², Minrui He¹^,², Yangxun Pan¹^,², Juncheng Wang¹^,², Jinbin Chen¹^,², Zhongguo Zhou¹^,²^,^†()

¹State Key Laboratory of Cancer Prevention and Treatment in South China, Clinical Research Center for Malignant Tumors of Guangdong Province, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
²Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China

Received:2025-02-12 Published:2025-08-10
Corresponding author: Zhongguo Zhou

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引用本文：

吴添庆, 郑梽楷, 贺珉睿, 潘扬勋, 王骏成, 陈锦滨, 周仲国. 华蟾素治疗肝癌肝动脉灌注化疗术后疼痛的疗效和安全性[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(04): 569-575.

Tianqing Wu, Zhikai Zheng, Minrui He, Yangxun Pan, Juncheng Wang, Jinbin Chen, Zhongguo Zhou. Efficacy and safety of cinobufotalin in treatment of pain after hepatic arterial infusion chemotherapy for primary liver cancer[J/OL]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2025, 14(04): 569-575.

目的

探讨华蟾素治疗原发性肝癌（肝癌）肝动脉灌注化疗（HAIC）患者术后疼痛的疗效与安全性。

方法

回顾性分析2021年9月至2024年1月在中山大学肿瘤防治中心接受HAIC治疗的161例肝癌患者临床资料。患者均签署知情同意书，符合医学伦理学规定。其中男152例，女9例；年龄27~74岁，中位年龄54岁。根据是否接受华蟾素治疗，将患者分为华蟾素组（71例）与对照组（90例）。采用视觉模拟评分（VAS）评估患者疼痛程度。两组患者中重度疼痛发生、止痛药物使用情况比较采用χ²检验，采用森林图分析不同因素对华蟾素治疗中重度疼痛的影响；两组Plt和肝功能等指标比较采用t检验或Mann-Whitney U检验。

结果

HAIC治疗后24~48 h，华蟾素组的中重度疼痛发生率为6%（4/71），明显低于对照组18%（16/90）（χ²=4.30，P=0.04），HAIC治疗后24 h内，华蟾素组和对照组中重度疼痛发生率分别为37%（26/71）、36%（32/90），差异无统计学意义（χ²=0.00，P>0.05）。森林图亚组分析显示，HAIC治疗后24~48 h，男性、年龄>50岁、HBsAg阳性、ALT >50 U/L、AST >40 U/L、TB>17.1 μmol/L、不使用碘化油、肿瘤直径>10 cm、无门脉癌栓、ALBI分级2~3级患者中，华蟾素组中重度疼痛发生率明显低于对照组（OR=0.88，0.87，0.88，0.80，0.84，0.80，0.80，0.85，0.90，0.83；P<0.05），HAIC治疗后，两组止痛药物使用、Plt与肝功能指标变化、不良反应发生情况比较差异均无统计学意义（P>0.05）。

结论

HAIC联合华蟾素治疗能够降低肝癌患者晚期中重度疼痛的发生率，改善患者的生活质量，提高患者对治疗的依从性。

关键词: 华蟾素, 癌，肝细胞, 肝动脉灌注化疗, 疼痛, 血小板

Objective

To evaluate the efficacy and safety of cinobufotalin in the treatment of postoperative pain in patients with primary liver cancer (PLC) undergoing hepatic arterial infusion chemotherapy (HAIC).

Methods

Clinical data of 161 PLC patients treated with HAIC in Sun Yat-sen University Cancer Center from September 2021 to January 2024 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 152 patients were male and 9 female, aged from 27 to 74 years, with a median age of 54 years. All patients were divided into the cinobufotalin group (n=71) and control group (n=90) according to whether they received cinobufotalin treatment. The degree of pain was assessed by visual analogue scale (VAS). The incidence of moderate and severe pain and use of analgesic drugs between two groups were compared by Chi-square test. The effect of different factors on cinobufotalin in the treatment of moderate and severe pain was analyzed by forest plot. The changes of platelet (Plt) count and liver function indexes between two groups were compared by t-test or Mann-Whitney U test.

Results

At 24-48 h after HAIC, the incidence of moderate and severe pain in the cinobufotalin group was 6% (4/71), significantly lower than 18% (16/90) in the control group (χ²=4.30, P=0.04). Within 24 h after HAIC, the incidence of moderate and severe pain in the cinobufotalin and control groups was 37% (26/71) and 36% (32/90), respectively, and the difference was not statistically significant (χ²=0.00, P>0.05). Forest plot subgroup analysis showed that the incidence of severe pain at 24-48 h after HAIC among male patients, aged 50 years, positive HBsAg, ALT>50 U/L, AST>40 U/L, TB>17.1 μmol/L, no use of iodized oil, lesion size>10 cm, no portal vein tumor thrombus and albumin-bilirubin (ALBI) in the cinobufotalin group was significantly lower than that in the control group (OR=0.88, 0.87, 0.88, 0.80, 0.84, 0.80, 0.80, 0.85, 0.90, 0.83; all P<0.05). After HAIC, no significant difference was observed in the use of analgesic drugs, the changes of Plt and liver function indexes and the incidence of adverse reactions between two groups (all P>0.05).

Conclusions

HAIC combined with cinobufotalin can reduce the incidence of moderate and severe pain, improve the quality of life and enhance the compliance with treatment in patients with PLC.

Key words: Cinobufacini, Carcinoma,hepatocellular, Hepatic arterial infusion chemotherapy (HAIC), Pain, Platelet

表1 华蟾素组与对照组行HAIC治疗肝癌患者一般临床资料比较

临床特征	对照组	华蟾素组	统计值	P值
年龄(岁,±s)	53±11	54±9	t=-0.89	0.37
性别(例,男/女)	83/7	69/2	χ²=1.03	0.31
肝硬化(例)	31	27	χ²=0.09	0.76
HBsAg阳性(例)	73	62	χ²=0.72	0.40
奥沙利铂剂量(例)			χ²=0.31	0.58
85 mg/m²	38	34
130 mg/m²	52	37
使用碘化油(例)	54	31	χ²=3.62	0.06
Plt(×10⁹/L,±s)	216±96	205±104	t=0.68	0.50
ALT[U/L,M(Q₁,Q₃)]	36 (26,54)	37 (29,59)	Z=-1.16	0.24
AST[U/L,M(Q₁,Q₃)]	48 (37,73)	47 (37,68)	Z=-0.16	0.87
TB[μmol/L,M(Q₁,Q₃)]	12 (9,17)	13 (9,15)	Z=-0.26	0.79
ALB(g/L,±s)	40±4	40±5	t=0.69	0.49
PT(s,±s)	12.3±1.4	12.2±1.0	t=0.85	0.40
AFP [μg/L,M(Q₁,Q₃)]	140(10,3 410)	136(18,4 402)	Z=-0.58	0.56
PIVKA-Ⅱ [AU/L,M(Q₁,Q₃)]	1 462(159,17 242)	2 011(164,17 286)	Z=-0.51	0.61
肿瘤直径(cm,±s)	10±10	9±4	t=0.57	0.57
肿瘤多发(例)	59	48	χ²=0.01	0.92
癌栓(例)	53	35	χ²=1.11	0.29
癌栓位置(例)			χ²=2.00	0.37
门静脉	40	22
肝静脉	1	2
门静脉+肝静脉	12	11
Child-Pugh A级(例)	86	67	χ²=0.00	>0.99
BCLC分期(例,A/B/C)	14/14/62	15/18/38	χ²=4.11	0.13
ALBI分级(例, 1/2/3)	55/34/1	45/25/1	χ²=0.13	0.94

表1 华蟾素组与对照组行HAIC治疗肝癌患者一般临床资料比较

临床特征	对照组	华蟾素组	统计值	P值
年龄(岁,±s)	53±11	54±9	t=-0.89	0.37
性别(例,男/女)	83/7	69/2	χ²=1.03	0.31
肝硬化(例)	31	27	χ²=0.09	0.76
HBsAg阳性(例)	73	62	χ²=0.72	0.40
奥沙利铂剂量(例)			χ²=0.31	0.58
85 mg/m²	38	34
130 mg/m²	52	37
使用碘化油(例)	54	31	χ²=3.62	0.06
Plt(×10⁹/L,±s)	216±96	205±104	t=0.68	0.50
ALT[U/L,M(Q₁,Q₃)]	36 (26,54)	37 (29,59)	Z=-1.16	0.24
AST[U/L,M(Q₁,Q₃)]	48 (37,73)	47 (37,68)	Z=-0.16	0.87
TB[μmol/L,M(Q₁,Q₃)]	12 (9,17)	13 (9,15)	Z=-0.26	0.79
ALB(g/L,±s)	40±4	40±5	t=0.69	0.49
PT(s,±s)	12.3±1.4	12.2±1.0	t=0.85	0.40
AFP [μg/L,M(Q₁,Q₃)]	140(10,3 410)	136(18,4 402)	Z=-0.58	0.56
PIVKA-Ⅱ [AU/L,M(Q₁,Q₃)]	1 462(159,17 242)	2 011(164,17 286)	Z=-0.51	0.61
肿瘤直径(cm,±s)	10±10	9±4	t=0.57	0.57
肿瘤多发(例)	59	48	χ²=0.01	0.92
癌栓(例)	53	35	χ²=1.11	0.29
癌栓位置(例)			χ²=2.00	0.37
门静脉	40	22
肝静脉	1	2
门静脉+肝静脉	12	11
Child-Pugh A级(例)	86	67	χ²=0.00	>0.99
BCLC分期(例,A/B/C)	14/14/62	15/18/38	χ²=4.11	0.13
ALBI分级(例, 1/2/3)	55/34/1	45/25/1	χ²=0.13	0.94

图1 不同因素对华蟾素组和对照组肝癌患者HAIC治疗24~48 h中重度疼痛疗效影响分析的森林图注：对照组90例，华蟾素组71例；HAIC为肝动脉灌注化疗，BCLC分期为巴塞罗那临床肝癌分期，ALBI为白蛋白-胆红素

表2 肝癌HAIC治疗过程中华蟾素组与对照组止痛药物使用比较[例（%）]

组别	例数	使用止痛药物	使用阿片类药物
华蟾素组	71	25(35)	18(25)
对照组	90	29(32)	23(26)
χ²值		0.05	0.00
P值		0.82	>0.99

表2 肝癌HAIC治疗过程中华蟾素组与对照组止痛药物使用比较[例（%）]

组别	例数	使用止痛药物	使用阿片类药物
华蟾素组	71	25(35)	18(25)
对照组	90	29(32)	23(26)
χ²值		0.05	0.00
P值		0.82	>0.99

图2 HAIC治疗前后华蟾素组与对照组肝癌患者实验室指标变化比较注：HAIC为肝动脉灌注化疗

表3 肝癌HAIC治疗过程中华蟾素组与对照组不良反应发生情况比较[例（%）]

不良反应	对照组	华蟾素组	χ²值	P值
发热	21(23)	17(24)	0.00	>0.99
腹部不适	35(39)	25(35)	0.10	0.75
恶心呕吐	33(37)	28(39)	0.04	0.84
过敏	2(2)	2(3)	0.00	>0.99
总体	62(69)	44(62)	0.56	0.45

表3 肝癌HAIC治疗过程中华蟾素组与对照组不良反应发生情况比较[例（%）]

不良反应	对照组	华蟾素组	χ²值	P值
发热	21(23)	17(24)	0.00	>0.99
腹部不适	35(39)	25(35)	0.10	0.75
恶心呕吐	33(37)	28(39)	0.04	0.84
过敏	2(2)	2(3)	0.00	>0.99
总体	62(69)	44(62)	0.56	0.45

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Efficacy and safety of cinobufotalin in treatment of pain after hepatic arterial infusion chemotherapy for primary liver cancer

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Efficacy and safety of cinobufotalin in treatment of pain after hepatic arterial infusion chemotherapy for primary liver cancer