Effect of afatinib combined with pemetrexed and carboplatin chemotherapy in patients with gefitinib resistant lung adenocarcinoma

doi:10.3760/cma.j.issn.1007-1245.2024.16.009

Abstract

Abstract:

Objective　To investigate the clinical effect of afatinib combined with pemetrexed and carboplatin chemotherapy in patients with gefitinib resistant lung adenocarcinoma. Methods　A total of 84 patients with gefitinib-resistant lung adenocarcinoma admitted to Shangqiu First People's Hospital from January 2021 to December 2022 were selected and were divided into an observation group (42 cases) and a control group (42 cases) according to the random number table method. In the control group, there were 24 males and 18 females, the age was 37-68 (52.58±2.21) years old, the body mass index (BMI) was 18-27 (23.11±1.17) kg/m², the lesions were at left upper in 18 cases, left lower in 16 cases, right upper in 5 cases, and right lower in 3 cases, and the clinical stage was stage III in 20 cases and stage IV in 22 cases. In the observation group, there were 21 males and 21 females, the age was 37-68 (52.67±2.24) years old, the BMI was 18-27 (23.06±1.14) kg/m², the lesions were at left upper in 17 cases, left lower in 14 cases, right upper in 5 cases, and right lower in 6 cases, and the clinical stage was stage III in 18 cases and stage IV in 24 cases. The control group received pemetrexed and carboplatin chemotherapy, and the observation group received afatinib treatment on the basis of the control group. Both groups were treated for 2 courses. The therapeutic effect, tumor markers [carbohydrate antigen 199 (CA199), carcinoembryonic antigen (CEA), and neuron-specific enolase (NSE)], immune function (T lymphocyte subsets CD3⁺, CD4⁺, and CD8⁺), and adverse reactions were compared between the two groups. Independent sample t test and χ² test were used. Results　The total effective rate of the observation group [76.19% (32/42)] was higher than that of the control group [52.38% (22/42)] (P<0.05). After treatment, the levels of CA199 [(44.39±3.88) μg/L], NSE [(13.45±1.22) μg/L], and CEA [(6.17±0.57) μg/L] in the observation group were lower than those in the control group [(61.02±5.24) μg/L, (18.69±1.74) μg/L, and (9.26±0.81) μg/L] (all P<0.05). After treatment, the levels of CD3⁺ [(65.39±5.22)%] and CD4⁺ [(36.15±2.71)%] in the observation group were higher than those in the control group [(57.69±4.38)% and (31.58±2.64)%], but the level of CD8⁺ [(27.16±1.53)%] was lower than that in the control group [(30.87±2.07)%] (all P<0.05). During treatment, there was no statistically significant difference in the total incidence of adverse reactions between the observation group [26.19% (11/42)] and the control group [19.05% (8/42)] (P>0.05). Conclusion　Afatinib combined with pemetrexel and carboplatin chemotherapy has a significant therapeutic effect in patients with gefitinib-resistant lung adenocarcinoma, which can reduce the levels of tumor markers and the damage on immune function, and has high safety.

Key words:

Lung adenocarcinoma, Gefitinib-resistant, Afatinib, Pemetrexed, Carboplatin, Chemotherapy

摘要：

目的　探讨阿法替尼联合培美曲塞和卡铂化疗方案在吉非替尼耐药肺腺癌患者中的临床效果。方法　选取2021年1月至2022年12月在商丘市第一人民医院治疗的吉非替尼耐药肺腺癌患者84例，采用随机数字表法将患者分为观察组（42例）和对照组（42例）。对照组男24例，女18例；年龄37～68（52.58±2.21）岁；体重指数（BMI）18～27（23.11±1.17）kg/m²；病灶：左上18例，左下16例，右上5例，右下3例；临床分期：Ⅲ期20例，Ⅳ期22例；采用培美曲塞和卡铂化疗。观察组男21例，女21例；年龄37～68（52.67±2.24）岁；BMI 18～27（23.06±1.14）kg/m²；病灶：左上17例，左下14例，右上5例，右下6例；临床分期：Ⅲ期18例，Ⅳ期24例；在对照组的基础上接受阿法替尼治疗。两组患者均持续治疗2个疗程。比较两组的治疗效果、肿瘤标志物水平［糖类抗原199（CA199）、癌胚抗原（CEA）、神经烯醇化酶（NSE）］、免疫功能（T淋巴细胞亚群CD3⁺、CD4⁺、CD8⁺）、不良反应发生情况。采用独立样本t检验和χ²检验。结果　观察组总有效率［76.19%（32/42）］高于对照组［52.38%（22/42）］（P<0.05）。治疗后，观察组CA199［（44.39±3.88）μg/L］、NSE［（13.45±1.22）μg/L］、CEA［（6.17±0.57）μg/L］水平均低于对照组［（61.02±5.24）μg/L、（18.69±1.74）μg/L、（9.26±0.81）μg/L］（均P<0.05）。治疗后，观察组CD3⁺［（65.39±5.22）%］、CD4⁺［（36.15±2.71）%］水平均高于对照组［（57.69±4.38）%、（31.58±2.64）%］，CD8⁺［（27.16±1.53）%］水平低于对照组［（30.87±2.07）%］（均P<0.05）。治疗期间，观察组不良反应总发生率［26.19%（11/42）］和对照组［19.05%（8/42）］比较，差异无统计学意义（P>0.05）。结论　阿法替尼联合培美曲塞和卡铂化疗方案在吉非替尼耐药肺腺癌患者中的治疗效果显著，可降低肿瘤标志物水平，减轻免疫功能的损伤，具有较高的安全性。

关键词:

肺腺癌, 吉非替尼耐药, 阿法替尼, 培美曲塞, 卡铂, 化疗

Zhai Tingting, Wang Feng.

Effect of afatinib combined with pemetrexed and carboplatin chemotherapy in patients with gefitinib resistant lung adenocarcinoma [J]. International Medicine and Health Guidance News, 2024, 30(16): 2678-2681.

翟婷婷王峰.

阿法替尼联合培美曲塞和卡铂化疗方案在吉非替尼耐药肺腺癌患者中的应用效果 [J]. 国际医药卫生导报, 2024, 30(16): 2678-2681.

References

[1] 贾亚辉,宋小珍,曾祥学,等.同步放化疗治疗局部晚期非小细胞肺癌的效果及对免疫功能和血清EGFR、TGF-α水平的影响[J].中国实用医刊,2023,50(12):47-50.DOI:10.3760/cma.j.cn115689-20230316-01660.
[2] Urbán L, Dóczi R, Vodicska B, et al. Major clinical response to afatinib monotherapy in lung adenocarcinoma harboring EGFR exon 20 insertion mutation[J]. Clin Lung Cancer, 2021, 22(1):e112-e115. DOI: 10.1016/j.cllc.2020. 09.005.
[3] 任绮.培美曲塞联合卡铂治疗吉非替尼耐药肺腺癌40例效果及毒副反应观察[J].药品评价,2021,18(12):763-765.DOI:10.19939/j.cnki.1672-2809.2021.12.19.
[4] 马桂凯.培美曲塞、卡铂联合吉非替尼治疗晚期肺腺癌的临床研究[J].当代医药论丛,2020,18(17):180-181.DOI:10.3969/j.issn.2095-7629.2020.17.137.
[5] 郭田田.替雷利珠单抗联合培美曲塞、卡铂化疗方案对肺腺癌患者肿瘤标志物、免疫功能及炎症因子的影响[J].淮海医药,2023,41(5):509-512.DOI:10.14126/j.cnki.1008- 7044.2023.05.018.
[6] 陈越平.吉非替尼与含铂类化疗联合时序对EGFR突变型肺腺癌患者的临床疗效对比[J].实用癌症杂志,2018,33(6):927-930.DOI:10.3969/j.issn.1001-5930.2018.06.018.
[7] 亓妍文,LALLOO M.B.IBRAHIM,王丽萍.培美曲塞或多西他赛联合卡铂治疗吉非替尼耐药的晚期肺腺癌患者的疗效[J].郑州大学学报(医学版),2020,55(2):192-195.DOI:10.13705/j.issn.1671-6825.2019.11.016.
[8] 郭玺,罗煜,付海艳,等.吉非替尼联合培美曲塞和顺铂在EGFR突变晚期肺腺癌中的近期疗效和安全性观察[J].中国医学创新,2020,17(10):129-132.DOI:10.3969/j.issn.1674-4985.2020.10.032.
[9] 薛英杰,贾靖,吴杨,等.阿法替尼分别联合培美曲塞、吉西他滨治疗非小细胞肺癌的临床研究[J].空军医学杂志,2019,35(1):28-31.DOI:10.3969/j.issn.2095-3402.2019. 01.009.
[10] 中华医学会放射肿瘤治疗学分会,中国医师协会放射肿瘤治疗医师分会,中国抗癌协会放射治疗专业委员会,等.中国非小细胞肺癌放射治疗临床指南(2020版)[J].中华放射肿瘤学杂志,2020,29(8):599-607.DOI:10.3760/cma.j.cn113030-20200528-00284.
[11] 张云江.培美曲塞联合顺铂和吉非替尼治疗晚期肺腺癌的临床疗效和毒副反应[J].实用临床医药杂志,2016,20(17):145-146,149.DOI:10.7619/jcmp.201617051.
[12] 王小璞,宋璟,戴诗蕾,等.温肾宁血方对非小细胞肺癌化疗患者骨髓抑制的效果及对INF-γ、CD4+/CD8+T细胞比值的影响[J].国际医药卫生导报,2021,27(21):3354-3357.DOI:10.3760/cma.j.issn.1007-1245.2021.21.018.
[13] 薛凌飞,雷彬花.吉非替尼联合培美曲塞和卡铂化疗方案治疗晚期非小细胞肺癌的效果[J].临床医学,2020,40(11):95-96.DOI:10.19528/j.issn.1003-3548.2020.11.038.
[14] Aguiar PN, Haaland B, Park W, et al. Cost-effectiveness of osimertinib in the first-line treatment of patients with EGFR-mutated advanced non-small cell lung cancer[J]. JAMA Oncol, 2018, 4(8):1080-1084. DOI: 10.1001/jamaoncol.2018.1395.
[15] 杨珺,陈伟,李国辉.中国非小细胞肺癌患者培美曲塞联合卡铂化疗剂量的影响因素[J].临床药物治疗杂志,2018,16(6):56-60,65.DOI:10.3969/j.issn.1672-3384.2018. 06.014.
[16] 宋琳.吉非替尼联合培美曲塞与卡铂治疗老年晚期EGFR突变型非小细胞肺癌患者的效果[J].慢性病学杂志,2022,23(8):1250-1252.DOI:10.16440/J.CNKI.1674-8166.2022. 08.36.
[17] 马东阳,耿良,胡彦辉,等.培美曲塞与顺铂配伍治疗晚期肺腺癌的疗效与安全性分析[J].国际医药卫生导报,2016,22(21):3297-3299.DOI:10.3760/cma.j.issn.1007-1245. 2016.21.028.
[18] 范群,伍小平,戴文香,等.培美曲塞与铂类化疗药联合使用对晚期肺腺癌患者治疗有效性与安全性研究[J].东南大学学报(医学版),2017,36(5):723-728.DOI:10.3969/j.issn.1671-6264.2017.05.008.
[19] 张惠,时建明,张勤英,等.培美曲塞联合卡铂化疗后培美曲塞维持治疗晚期肺腺癌的临床研究[J].实用癌症杂志,2017,32(12):1987-1989.DOI:10.3969/j.issn.1001-5930. 2017.12.022.
[20] 李宏庆,唐中豪,李向阳,等.培美曲塞联合顺铂或卡铂治疗晚期老年肺腺癌的临床对照研究[J].老年医学与保健,2016,22(3):146-148.DOI:10.3969/j.issn.1008-8296. 2016.03.05.
[21] 黄法臣.阿法替尼分别联合培美曲塞、吉西他滨对非小细胞肺癌患者不良反应及生活质量的影响[J].中国保健营养,2019,29(26):265-266.
[22] 姜伟华,高永山,容宇,等.阿法替尼与埃克替尼联合TP化疗治疗晚期EGFR突变型非小细胞肺癌的比较研究[J].现代药物与临床,2023,38(1):142-146.DOI:10.7501/j.issn.1674-5515.2023.01.023.
[23] Hu X, Shi S, Wang H, et al. Blocking autophagy improves the anti-tumor activity of afatinib in lung adenocarcinoma with activating EGFR mutations in vitro and in vivo[J]. Sci Rep, 2017, 7(1):4559. DOI: 10.1038/s41598-017- 04258-8.
[24] 王小文,谢金龙,朱晓芸,等.阿法替尼联合培美曲塞和卡铂化疗治疗吉非替尼耐药肺腺癌患者的临床效果[J].广西医学,2022,44(1):29-33,45.DOI:10.11675/j.issn.0253-4304. 2022.01.07.
[25] 刘炎华,马娜.阿法替尼联合化疗治疗EGFR突变晚期非小细胞肺癌的临床效果[J].临床合理用药杂志,2022,15(31):23-26,30.DOI:10.15887/j.cnki.13-1389/r.2022.31.007.