帕博利珠单抗联合XELOX方案治疗晚期胃癌的回顾性研究

冯惠枝; 柳婧美; 卜晓倩

doi:10.19401/j.cnki.1007-3639.2024.11.005

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帕博利珠单抗联合XELOX方案治疗晚期胃癌的回顾性研究

论著 | 更新时间：2025-12-31

- 帕博利珠单抗联合XELOX方案治疗晚期胃癌的回顾性研究
- A retrospective study of pembrolizumab combined with XELOX regimen in the treatment of advanced gastric cancer
- 中国癌症杂志 2024年34卷第11期页码：1028-1035
- 作者机构：
  
  1. 山西省肿瘤医院、中国医学科学院肿瘤医院山西医院、山西医科大学附属肿瘤医院消化内科，山西太原 030013
  2. 山西白求恩医院消化系统肿瘤科，山西太原 030012
- 作者简介：
  
  冯惠枝（ORCID: 0009-0009-2095-5334），硕士，主治医师。
- 基金信息：
  
  山西省医师协会医师科研项目(YSXH-QL2023XH001)
- DOI：10.19401/j.cnki.1007-3639.2024.11.005
  中图分类号： R735.2
- 收稿：2024-06-05，
  
  修回：2024-08-24，
  
  纸质出版：2024-11-30
- 稿件说明：
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冯惠枝, 柳婧美, 卜晓倩. 帕博利珠单抗联合XELOX方案治疗晚期胃癌的回顾性研究[J]. 中国癌症杂志, 2024,34(11):1028-1035.

Huizhi FENG, Jingmei LIU, Xiaoqian BU. A retrospective study of pembrolizumab combined with XELOX regimen in the treatment of advanced gastric cancer[J]. China Oncology, 2024, 34(11): 1028-1035.
冯惠枝, 柳婧美, 卜晓倩. 帕博利珠单抗联合XELOX方案治疗晚期胃癌的回顾性研究[J]. 中国癌症杂志, 2024,34(11):1028-1035. DOI： 10.19401/j.cnki.1007-3639.2024.11.005.

Huizhi FENG, Jingmei LIU, Xiaoqian BU. A retrospective study of pembrolizumab combined with XELOX regimen in the treatment of advanced gastric cancer[J]. China Oncology, 2024, 34(11): 1028-1035. DOI： 10.19401/j.cnki.1007-3639.2024.11.005.

摘要

背景与目的：

尽管目前针对胃癌的治疗手段已取得了显著进步，但晚期胃癌患者仍存在预后差、5年生存率偏低等问题，因此探究有效的治疗方案仍是临床研究的重点。帕博利珠单抗作为新型免疫检查点抑制剂，其临床应用效果及安全性仍需大量研究予以验证，因此本研究回顾性分析帕博利珠单抗联合XELOX方案治疗晚期胃癌的效果，以期为临床治疗提供参考。

方法：

回顾性收集2020年3月—2022年8月山西省肿瘤医院收治的晚期胃癌患者的临床资料。纳入标准：经临床组织病理学检查确诊为HER2阴性、未经治疗的晚期胃癌/食管胃结合部腺癌患者，符合相关诊断标准；TNM分期为Ⅳ期；年龄≥20岁；预计生存期≥6个月；治疗前器官无严重损伤者；Karnofsky评分

60分；临床

资料完整者。排除标准：合并重要器官功能障碍者；合并甲状腺功能减退或亢进者；合并血液、凝血功能异常者；合并自身免疫性疾病者；哺乳、妊娠期女性；存在精神类疾病或诊断史者；伴有其他恶性肿瘤者；存在严重肝肾功能障碍者；临床资料不全者。通过纳入和排除标准选择91例晚期胃癌患者，其中45例接受XELOX方案治疗（对照组），46例接受帕博利珠单抗联合XELOX方案治疗（观察组），建立数据库后发现观察组1例患者的治疗信息存在逻辑错误，因此去除该病例，最终确定研究对象90例，对照组和观察组各45例。对比两组疗效、中位总生存期（overall survival，OS）、中位无进展生存期（progression-free survival，PFS）、不良反应、生活质量改善情况，以及治疗前后癌胚抗原（carcinoembryonic antigen，CEA）、糖类抗原19-9（carbohydrate antigen 19-9，CA19-9）、大肠杆菌、双歧杆菌、乳杆菌水平。本研究已获得山西省肿瘤医院伦理委员会批准（伦理编号：KY2023081）。

结果：

治疗后观察组疾病进展（progressive disease，PD）占20.0%（9/45），低于对照组的40.0%（18/45），但两组的疾病稳定（stable disease，SD）、完全缓解（complete response，CR）和部分缓解（partial response，PR）占比差异无统计学意义（

0.05）。治疗后观察组的生活质量改善率为60.0%（27/45），高于对照组的37.8%（17/45）（

0.05）。观察组的中位OS和中位PFS均大于对照组（

0.05）。治疗后观察组的外周血CEA、CA19-9均低于对照组（

0.05）。治疗后观察组的大肠杆菌数量低于对照组，双歧杆菌、乳杆菌数量均高于对照组（

0.05）。两组不同等级恶心呕吐、腹泻、白细胞减少、皮疹及肝功能损害的发生率差异无统计学意义（

0.05）。

结论：

帕博利珠单抗联合XELOX方案可调节肿瘤标志物在晚期胃癌患者中的水平，预防疾病进展，改善患者生活质量，还有助于维持肠道微生态平衡。

Abstract

Background and purpose:

Despite the significant advancements that have been made in the treatment of gastric cancer

there are still problems such as poor prognosis and low five-year survival rate in advanced gastric cancer. Therefore

exploring effective treatment options remains a key focus of clinical research. As a new type of immune checkpoint inhibitor

the clinical efficacy and safety of pembrolizumab still need to be confirmed by extensive research. Therefore

this study conducted regression analysis of the effect of pembrolizumab combined with XELOX regimen in the treatment of advanced gastric cancer

providing a reference for clinical treatment.

Methods:

Clinical data of patients with advanced gastric cancer who were admitted to Shanxi Province Cancer Hospital from March 2020 to August 2022 were retrospectively collected. Inclusion criteria: pa

tients with HER2-negative

untreated advanced gastric cancer or adenocarcinoma of the esophagogastric junction

confirmed by clinical histopathological examination and meeting relevant diagnostic criteria; TNM stage Ⅳ; age ≥20 years; expected survival ≥6 months; no severe organ damage before treatment; Karnofsky score

60; patients with complete clinical data. Exclusion criteria: patients with concurrent major organ dysfunction; hypothyroidism or hyperthyroidism; blood or coagulation disorders; autoimmune diseases; lactating or pregnant women; individuals with mental illnesses or a history of mental illness; those with concurrent other malignancies; those with severe liver or kidney dysfunction; patients with incomplete clinical data. Based on the inclusion and exclusion criteria

91 patients with advanced gastric cancer were selected. Among them

45 received XELOX regimen treatment (control group)

and 46 received pembrolizumab combined with XELOX regimen treatment (observation group). After establishing the database

one patient in the observation group was found to have logical errors in their treatment information and was therefore excluded. Ultimately

90 patients were included in the study

with 45 in each of the control and observation groups. The efficacy

median overall survival (OS)

median progression-free survival (PFS)

toxic side effects

improvement in quality of life

and levels of carcinoembryonic antigen (CEA)

carbohydrate antigen 19-9 (CA19-9)

Escherichia coli

Bifidobacterium and Lactobacillus before and after treatment were compared between the two groups. This study was approved by the ethics committee of Shanxi Province Cancer Hospital (ethics number: KY2023081).

Results:

After treatment

the proportion of progressive disease (PD) in the observation group was 20.0% (9/45)

which was lower than that in the control group (40.0%

18/45). However

there was no significant difference between the two groups in proportion of stable disease (SD)

complete response (CR) and partia

l response (PR) (

0.05). The improvement rate of quality of life in the observation group after treatment was 60.0% (27/45)

which was higher than that in the control group

with a rate of 37.8% (17/45) (

0.05). The median OS and PFS in the observation group were longer compared with the control group (

0.05). After treatment

the levels of CEA and CA19-9 in peripheral blood of the observation group were lower compared with the control group (

0.05). After treatment

the number of Escherichia coli was lower in the observation group than in the control group

while the numbers of Bifidobacterium and Lactobacillus were higher (

0.05). There was no significant difference in the incidence of nausea and vomiting

diarrhea

leukopenia

rash

liver function damage between the two groups (

0.05).

Conclusion:

The combination of pembrolizumab and XELOX regimen can regulate the expression levels of tumor markers in patients with advanced gastric cancer

prevent disease progression

improve patient quality of life

and help maintain intestinal microecology balance.

关键词

Keywords

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