中国临床药理学杂志

安罗替尼与培美曲塞及卡铂联合用药方案对获得性耐药晚期肺腺癌患者的临床研究

PDF下载

徐海洋 ^a , 汪霖 ^a , 李连涛 ^b

中国临床药理学杂志 | 临床与基础桥接研究 2025,41(20): 2856-2862

收起

中国临床药理学杂志 |临床与基础桥接研究 2025 , 41 (20) : 2856 -2862

安罗替尼与培美曲塞及卡铂联合用药方案对获得性耐药晚期肺腺癌患者的临床研究

全屏

[Author(id=1292439992702366718, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1292439989808296948, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1292439992828195840, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1292439989808296948, authorId=1292439992702366718, language=EN, stringName=Hai-yang XU, firstName=Hai-yang, middleName=null, lastName=XU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=^a, address=^a.Department of Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1292439992907886592, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1292439989808296948, authorId=1292439992702366718, language=CN, stringName=徐海洋, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=^a, address=^a.徐州医科大学附属医院，肿瘤科，江苏徐州 221002, bio={"content":"

徐海洋（1980-），男，副主任医师，主要从事肿瘤方面的临床工作研究

"}, bioImg=null, bioContent=

徐海洋（1980-），男，副主任医师，主要从事肿瘤方面的临床工作研究

, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1292439992350045175, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1292439989808296948, xref=a., ext=[AuthorCompanyExt(id=1292439992362628088, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1292439989808296948, companyId=1292439992350045175, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=^a.Department of Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China), AuthorCompanyExt(id=1292439992375211001, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1292439989808296948, companyId=1292439992350045175, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=^a.徐州医科大学附属医院，肿瘤科，江苏徐州 221002)])]), Author(id=1292439992995966978, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1292439989808296948, orderNo=1, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1292439993063075844, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1292439989808296948, authorId=1292439992995966978, language=EN, stringName=Lin WANG, firstName=Lin, middleName=null, lastName=WANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=^a, address=^a.Department of Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1292439993130184709, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1292439989808296948, authorId=1292439992995966978, language=CN, stringName=汪霖, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=^a, address=^a.徐州医科大学附属医院，肿瘤科，江苏徐州 221002, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1292439992350045175, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1292439989808296948, xref=a., ext=[AuthorCompanyExt(id=1292439992362628088, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1292439989808296948, companyId=1292439992350045175, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=^a.Department of Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China), AuthorCompanyExt(id=1292439992375211001, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1292439989808296948, companyId=1292439992350045175, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=^a.徐州医科大学附属医院，肿瘤科，江苏徐州 221002)])]), Author(id=1292439993193099271, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1292439989808296948, orderNo=2, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=xzxhyxhy@163.com, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1292439993260208137, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1292439989808296948, authorId=1292439993193099271, language=EN, stringName=Lian-tao LI, firstName=Lian-tao, middleName=null, lastName=LI, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=^b, address=^b.Department of Radiotherapy, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1292439993335705610, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1292439989808296948, authorId=1292439993193099271, language=CN, stringName=李连涛, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=^b, address=^b.徐州医科大学附属医院，肿瘤放疗科，江苏徐州 221002, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1292439992463291386, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1292439989808296948, xref=b., ext=[AuthorCompanyExt(id=1292439992471679995, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1292439989808296948, companyId=1292439992463291386, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=^b.Department of Radiotherapy, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China), AuthorCompanyExt(id=1292439992622674940, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1292439989808296948, companyId=1292439992463291386, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=^b.徐州医科大学附属医院，肿瘤放疗科，江苏徐州 221002)])])]

徐海洋^a, 汪霖^a, 李连涛^b

作者信息

^a.徐州医科大学附属医院，肿瘤科，江苏徐州 221002

^b.徐州医科大学附属医院，肿瘤放疗科，江苏徐州 221002

通讯作者:

李连涛，副主任医师，硕士生导师 MP: 15895214389 E-mail: xzxhyxhy@163.com

作者简介:

徐海洋（1980-），男，副主任医师，主要从事肿瘤方面的临床工作研究

Clinical trail of the combination regimen of anlotinib with pemetrexed and carboplatin on immune regulation in patients with acquired drug-resistant advanced lung adenocarcinoma

Hai-yang XU^a, Lin WANG^a, Lian-tao LI^b

Affiliations

^a.Department of Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China

^b.Department of Radiotherapy, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China

出版时间: 2025-10-28 doi: 10.13699/j.cnki.1001-6821.2025.20.002

文章导航

摘要

收起

目的

观察安罗替尼胶囊与注射用培美曲塞及卡铂注射用联合用药方案对酪氨酸激酶抑制剂（TKI）获得性耐药晚期肺腺癌患者的临床疗效和安全性。

方法

将TKI获得性耐药晚期肺腺癌患者根据治疗方法分为对照组与试验组。对照组患者在各治疗周期的首日接受注射用培美曲塞二钠500 mg·m^-2+卡铂注射液（按照血药浓度-时间曲线下面积6 g·L^-1·min^-1计算）静脉输注治疗，每3 w为1个周期。在对照组基础上，试验组予以盐酸安罗替尼胶囊10 mg，每周期从第1天开始连续口服2 w，停药1 w，每3 w为1个周期。2组连续治疗4个周期以上。比较2组的临床疗效、肿瘤标志物水平、血管内皮生长因子（VEGF）水平、免疫功能和远期疗效并进行安全性评价。

结果

本研究共入组102例，对照组48例，试验组54例。治疗后，对照组和试验组的疾病控制率分别为64.58%（31例/48例）和83.33%（45例/54例），糖类抗原125水平分别为（52.38±7.21）和（48.49±6.12）U·mL^-1，癌胚抗原水平分别为（8.29±1.79）和（7.52±1.21）μg·L^-1，神经元特异性烯醇化酶水平分别为（26.17±4.33）和（23.84±3.32）μg·L^-1，VEGF-A水平分别为（95.38±10.76）和（89.47±11.32）pg·mL^-1，VEGF-B水平分别为（87.41±9.76）和（82.63±8.13）pg·mL^-1，VEGF-C水平分别为（61.56±7.49）和（58.67±6.20）pg·mL^-1，试验组上述指标与对照组比较，在统计学上差异均有统计学意义（均P<0.05）。对照组和试验组的不良反应总发生率分别为37.50%（18例/48例）和42.59%（23例/54例），中位无进展生存期分别为16和21个月，中位总生存期分别为22和34个月，上述指标2组间比较，在统计学上差异均无统计学意义（P>0.05）。

结论

TKI获得性耐药晚期肺腺癌患者在注射用培美曲塞、卡铂注射液的基础上加用安罗替尼胶囊，可显著增强疗效及免疫调节，同时抑制肿瘤生长，且安全性、远期疗效良好。

关键词

安罗替尼胶囊 / 注射用培美曲塞 / 卡铂注射液 / 酪氨酸激酶抑制剂 / 获得性耐药 / 肺腺癌

Abstract

收起

Objective

To observe the efficaly and safety of combination regimen of anlotinib with pemetrexed and carboplatin in patients with advanced lung adenocarcinoma with acquired resistance to tyrosine kinase inhibitor (TKI).

Methods

Patients with advanced lung adenocarcinoma with acquired TKI resistance were divided into control group and treatment group according to the treatment methods. Patients in the control group received intravenous infusions of pemetrexed disodium for injection (500 mg·m^-2) and carboplatin injection (dose cauculated based on area under the blood concentration-time curve 6 g·L^-1·min^-1) on the first day of each treatment cycle, with each 3 weeks as one cycle. On the basis of the control group, the treatment group was given anlotinib hydrochloride capsules, which were taken 10 mg orally continuously for 2 weeks starting from day 1 of each cycle, followed by a 1-week drug holiday. Each 3-week period constituted one treatment cycle. Both groups were continuously treated for 4 cycles or more. The therapeutic outcomes, tumor marker concentrations, and vascular endothelial growth factor (VEGF) levels, immune function, safety evaluation, and long-term efficacy were compared between the two groups.

Results

A total of 102 cases were enrolled; there were 48 cases in control group and 54 cases in treatment group. Disease control rate of control group and treatment group were 64.58% (31 cases/48 cases) and 83.33% (45 cases/54 cases), respectively; the carbohydrate antigen 125 levels were (52.38±7.21) and (48.49±6.12) U·mL^-1, respectively; the carcinoembryonic antigen levels were (8.29±1.79) and (7.52±1.21) μg·L^-1, respectively; the neuron-specific enolase levels were (26.17±4.33) and (23.84±3.32) μg·L^-1, respectively; the VEGF-A levels were (95.38±10.76) and (89.47±11.32) pg·mL^-1, respectively; the VEGF-B levels were (87.41±9.76) and (82.63±8.13) pg·mL^-1, respectively; and the VEGF-C levels were (61.56±7.49) and (58.67±6.20) pg·mL^-1, respectively. Comparison of all measured parameters in the treatment group and control group demonstrated statistically significant differences (all P<0.05). Adverse event rate of control group and treatment group were 37.50% (18 cases/48 cases) and 42.59% (23 cases/54 cases) respectively; median progression-free survival were 16 and 21 months, respectively; overall survival were 22 and 34 months, respectively; compared between 2 groups, the differences of the above indicators were not statistically significant (all P>0.05).

Conclusion

The addition of anlotinib to pemetrexed and carboplatin in patients with TKI-acquired resistant advanced lung adenocarcinoma significantly enhances the efficacy and immunomodulation, and inhibits the tumor growth at the same time, with a good safety profile and long-term efficacy.

Key words

anlotinib capsules / intravenous infusion of pemetrexed for injection / carboplatin injection / tyrosine kinase inhibitor / acquired resistance / lung adenocarcinoma

引用本文

徐海洋, 汪霖, 李连涛. 安罗替尼与培美曲塞及卡铂联合用药方案对获得性耐药晚期肺腺癌患者的临床研究. 中国临床药理学杂志, 2025 , 41 (20) : 2856 -2862 . DOI: 10.13699/j.cnki.1001-6821.2025.20.002

Hai-yang XU, Lin WANG, Lian-tao LI. Clinical trail of the combination regimen of anlotinib with pemetrexed and carboplatin on immune regulation in patients with acquired drug-resistant advanced lung adenocarcinoma[J]. Chinese Journal of Clinical Pharmacology, 2025 , 41 (20) : 2856 -2862 . DOI: 10.13699/j.cnki.1001-6821.2025.20.002

参考文献

收起

文献

收起

参考文献引证文献

排序方式：

2025年第41卷第20期

PDF下载

234

123

引用本文

BibTeX

文章信息

doi: 10.13699/j.cnki.1001-6821.2025.20.002

接收时间：2025-06-25
首发时间：2026-08-07
出版时间：2025-10-28

补充材料

相关文章

文章信息

作者

出版历史

收稿日期：2025-06-25

基金

作者信息

^a.徐州医科大学附属医院，肿瘤科，江苏徐州 221002

^b.徐州医科大学附属医院，肿瘤放疗科，江苏徐州 221002

通讯作者:

李连涛，副主任医师，硕士生导师 MP: 15895214389 E-mail: xzxhyxhy@163.com

参考文献

分享链接

https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2025.20.002

分享至

全文二维码

扫描看全文

引用本文

BibTeX

本文的引用情况

2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

关闭全屏

BibTeX
EndNote
RefWorks
TxT