替雷利珠单抗联合化疗治疗进展期食管癌的疗效及安全性

doi:10.3760/cma.j.cn371439-20250619-00004

摘要/Abstract

摘要：

目的回顾性分析替雷利珠单抗联合化疗治疗进展期食管癌的疗效和安全性。方法选择2021年3月至2024年6月江苏大学附属医院收治的128例进展期食管癌患者为研究对象，根据治疗方法不同分为常规组（n=60，采用紫杉醇脂质体+奈达铂治疗）和单抗组（n=68，采用紫杉醇脂质体+奈达铂+替雷利珠单抗治疗），以21 d为1个周期，共化疗4~6个周期，观察两组患者的近期疗效、肿瘤标志物和相关因子、炎症因子、免疫相关指标、生命质量相关评分和安全性。结果治疗后，单抗组客观缓解率（86.76%，59/68）高于常规组（65.00%，39/60），差异有统计学意义（χ²=8.42，P=0.004）。单抗组癌胚抗原（CEA）、细胞角质蛋白19片段抗原21-1（CYFRA21-1）、糖类抗原（CA）125、鳞状癌胚抗原（SCC-Ag）水平分别为（7.73±2.18）μg/L、（4.95±0.67）U/ml、（9.28±1.42）U/ml、（0.50±0.16）μg/L，常规组分别为（10.14±2.21）μg/L、（4.09±0.70）U/ml、（7.35±1.58）U/ml、（0.68±0.22）μg/L，差异均有统计学意义（t=6.20，P<0.001；t=7.10，P<0.001；t=7.28，P<0.001；t=5.34，P<0.001）；且两组患者治疗后CEA、CYFRA21-1、CA125、SCC-Ag水平均较治疗前显著降低（均P<0.05）。单抗组基质金属蛋白酶-9（MMP-9）、血管内皮生长因（VEGF）水平分别为（118.28±10.47）ng/ml、（320.27±18.79）ng/L，常规组分别为（126.75±14.51）ng/ml、（350.71±19.35）ng/L，差异均有统计学意义（t=3.82，P<0.001；t=9.02，P<0.001）；两组患者治疗后MMP-9、VEGF水平均较治疗前显著降低（均P<0.05）。单抗组白细胞介素（IL）-6、C反应蛋白（CRP）、肿瘤坏死因子-α（TNF-α）水平分别为（5.46±1.26）ng/L、（7.89±1.45）mg/L、（3.95±0.83）ng/L，常规组分别为（8.66±2.13）ng/L、（9.51±1.64）mg/L、（6.02±1.52）ng/L，差异均有统计学意义（t=10.49，P<0.001；t=5.93，P<0.001；t=9.71，P<0.001）；两组患者治疗后IL-6、CRP、TNF-α水平均较治疗前显著降低（均P<0.05）。单抗组T细胞亚群CD3⁺和CD4⁺/CD8⁺比值分别为（66.16±5.26）%、1.52±0.25，常规组分别为（58.41±5.17）%、1.15±0.27，差异均有统计学意义（t=8.39，P<0.001；t=8.05，P<0.001）；两组患者治疗后T细胞亚群CD3⁺和CD4⁺/CD8⁺比值均较治疗前显著增加（均P<0.05）。两组患者Karnofsky功能状态评分、安德森吞咽困难量表评分均较治疗前上升，且单抗组明显高于常规组；两组疼痛数字评定量表评分均下降，且单抗组明显低于常规组（均P<0.05）。两组患者常见不良反应为白细胞减少、恶心、乏力等，多数为1~2级，3级不良反应常规组发生率为10.00%（6/60），单抗组为20.59%（14/68），无4级不良反应发生；常规组不良反应总发生率（78.33%，47/60）与单抗组（75.00%，51/68）比较，差异无统计学意义（χ²=0.20，P=0.657）。结论与单独化疗比较，替雷利珠单抗联合化疗治疗进展期食管癌可提高近期疗效，安全性良好。

关键词: 食管肿瘤, 抗肿瘤联合化疗方案, 替雷利珠单抗

Abstract:

Objective To retrospectively analyze the efficacy and safety of tislelizumab combined with chemotherapy in the treatment of advanced esophageal cancer. Methods A total of 128 patients with advanced esophageal cancer admitted to the Affiliated Hospital of Jiangsu University from March 2021 to June 2024 were selected as the study subjects. According to different treatment methods， they were divided into a conventional group （n=60， treated with paclitaxel liposome+nedaplatin） and a monoclonal antibody group （n=68， treated with paclitaxel liposome+nedaplatin+tislelizumab）. With 21 days as one cycle， a total of 4-6 cycles of chemotherapy were administered. The short-term efficacy， tumor markers and related factors， inflammatory factors， immune related indicators， quality of life-related score and safety of the two groups of patients were observed. Results After treatment， the objective response rate in the monoclonal antibody group （86.76%， 59/68） was higher than that in the conventional group （65.00%， 39/60）， with a statistically significant difference （χ²=8.42， P=0.004）. The levels of carcinoembryonic antigen （CEA）， cytokeratin 19 fragment antigen 21-1 （CYFRA21-1）， carbohydrate antigen （CA） 125， and squamous cell carcinoma antigen （SCC-Ag） in the monoclonal antibody group were （7.73±2.18） μg/L，（4.95±0.67） U/ml，（9.28±1.42） U/ml， and （0.50±0.16） μg/L， respectively， and those in the conventional group were （10.14±2.21） μg/L，（4.09±0.70） U/ml，（7.35±1.58） U/ml， and （0.68±0.22） μg/L， respectively， with statistically significant differences （t=6.20， P<0.001； t=7.10， P<0.001； t=7.28， P<0.001； t=5.34， P<0.001）. Moreover， the levels of CEA， CYFRA21-1， CA125， and SCC-Ag in both groups of patients after treatment were significantly lower than those before treatment （all P<0.05）. The levels of matrix metalloproteinase-9 （MMP-9） and vascular endothelial growth factor （VEGF） in the monoclonal antibody group were （118.28±10.47） ng/ml and （320.27±18.79） ng/L， respectively， and those in the conventional group were （126.75±14.51） ng/ml and （350.71±19.35） ng/L， respectively， with statistically significant differences （t=3.82， P<0.001； t=9.02， P<0.001）. The levels of MMP-9 and VEGF in both groups of patients after treatment were significantly lower than those before treatment （all P<0.05）. The levels of interleukin （IL）-6， C-reactive protein （CRP） and tumor necrosis factor-α （TNF-α） in the monoclonal antibody group were （5.46±1.26） ng/L，（7.89±1.45） mg/L， and （3.95±0.83） ng/L， respectively， and those in the conventional group were （8.66±2.13） ng/L，（9.51±1.64） mg/L， and （6.02±1.52） ng/L， respectively， with statistically significant differences （t=10.49， P<0.001； t=5.93， P<0.001； t=9.71， P<0.001）. The levels of IL-6， CRP， and TNF-α in both groups of patients after treatment were significantly lower than those before treatment （all P<0.05）. The T-cell subsets CD3⁺ and CD4⁺/CD8⁺ ratio in the monoclonal antibody group were （66.16±5.26）% and 1.52±0.25， respectively， and those in the conventional group were （58.41±5.17）% and 1.15±0.27， respectively， with statistically significant differences （t=8.39， P<0.001； t=8.05， P<0.001）. The T-cell subsets CD3⁺ and CD4⁺/CD8⁺ ratio in both groups of patients after treatment were significantly higher than those before treatment （all P<0.05）. Compared with before treatment， the Karnofsky performance status scores and the M. D. Anderson dysphagia inventory scores of both groups of patients were increased， and the scores in the monoclonal antibody group were significantly higher than those in the conventional group； the numerical rating scale scores of both groups were decreased， and the score in the monoclonal antibody group was significantly lower than that in the conventional group （all P<0.05）. The common adverse reactions in the two groups were leukopenia， nausea， fatigue， etc.， most of which were grade 1-2. The incidence of grade 3 adverse reactions was 10.00%（6/60） in the conventional group and 20.59%（14/68） in the monoclonal antibody group. No grade 4 adverse reactions occurred. There was no statistically significant difference in the total incidence of adverse reactions between the conventional group （78.33%， 47/60） and the monoclonal antibody group （75.00%， 51/68； χ²=0.20， P=0.657）. Conclusions Compared with chemotherapy alone， tislelizumab combined with chemotherapy in the treatment of advanced esophageal cancer can improve short-term efficacy with good safety.

Key words: Esophageal neoplasms, Antineoplastic combined chemotherapy protocols, Tislelizumab

余云鹏, 戴春华, 凌锐. 替雷利珠单抗联合化疗治疗进展期食管癌的疗效及安全性[J]. 国际肿瘤学杂志, 2026, 53(1): 31-37.

Yu Yunpeng, Dai Chunhua, Ling Rui. Efficacy and safety of tislelizumab combined with chemotherapy in the treatment of advanced esophageal cancer[J]. Journal of International Oncology, 2026, 53(1): 31-37.

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项目	常规组（n=60）	单抗组（n=68）	t/χ²值	P值
性别（例）
男	35	36	0.38	0.540
女	25	32	0.38	0.540
年龄（岁，$ \bar{x} \pm s$）	51.52±9.81	50.22±10.14	0.74	0.464
TNM分期（例）
Ⅱ期	40	43	0.17	0.685
Ⅲ期	20	25	0.17	0.685
病理类型（例）
鳞状细胞癌	56	64	<0.01	>0.999
腺癌	4	4	<0.01	>0.999
既往治疗史（例）
无	45	53	0.15	0.695
有	15	15	0.15	0.695
后续治疗（例）
无	8	7	0.94	0.624
局部放疗	25	34
其他方案化疗	27	27

组别	CEA（μg/L）		CYFRA21-1（U/ml）		CA125（U/ml）		SCC-Ag（μg/L）
组别	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
常规组（n=60）	16.54±4.17	10.14±2.21^a	9.82±1.13	4.09±0.70^a	15.19±2.23	7.35±1.58^a	1.40±0.15	0.68±0.22^a
单抗组（n=68）	16.38±4.23	7.73±2.18^a	9.76±1.25	4.95±0.67^a	15.23±2.14	9.28±1.42^a	1.42±0.17	0.50±0.16^a
t值	0.22	6.20	0.28	7.10	0.10	7.28	0.70	5.34
P值	0.830	<0.001	0.780	<0.001	0.920	<0.001	0.480	<0.001

组别	MMP-9（ng/ml）		VEGF（ng/L）
组别	治疗前	治疗后	治疗前	治疗后
常规组（n=60）	142.35±24.18	126.75±14.51^a	410.24±19.66	350.71±19.35^a
单抗组（n=68）	140.19±26.53	118.28±10.47^a	406.86±20.47	320.27±18.79^a
t值	0.48	3.82	0.95	9.02
P值	0.633	<0.001	0.344	<0.001

组别	IL-6（ng/L）		CRP（mg/L）		TNF-α（ng/L）
组别	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
常规组（n=60）	15.32±3.31	8.66±2.13^a	15.25±1.69	9.51±1.64^a	12.21±2.16	6.02±1.52^a
单抗组（n=68）	15.21±3.16	5.46±1.26^a	15.49±1.11	7.89±1.45^a	12.06±2.10	3.95±0.83^a
t值	0.19	10.49	0.96	5.93	0.40	9.71
P值	0.848	<0.001	0.339	<0.001	0.691	<0.001

组别	CD3⁺（%）		CD4⁺/CD8⁺		KPS评分（分）		MDADI评分（分）		疼痛NRS评分（分）
组别	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
常规组（n=60）	53.28±4.41	58.41±5.17^a	0.88±0.22	1.15±0.27^a	71.22±2.15	74.47±2.50^a	40.29±4.82	55.76±5.23^a	4.57±1.23	3.15±0.92^a
单抗组（n=68）	53.16±4.69	66.16±5.26^a	0.84±0.21	1.52±0.25^a	71.45±2.36	80.11±2.43^a	39.85±4.14	68.35±4.99^a	4.66±1.15	1.86±0.73^a
t值	0.15	8.39	1.05	8.05	0.57	12.93	0.56	13.93	0.43	8.83
P值	0.882	<0.001	0.295	<0.001	0.567	<0.001	0.579	<0.001	0.670	<0.001