Therapeutic effect of antolini hydrochloride combined with docetaxel for elderly patients with NSCLC who took TP/PDL1 targeted chemotherapy and failed

doi:10.3760/cma.j.issn.1007-1245.2023.24.006

Abstract

Abstract:

Objective　To investigate the clinical efficacy and safety of antolini hydrochloride combined with docetaxel for elderly patients with non-small cell lung cancer (NSCLC) who took paclitaxel, cisplatin, and toralizumab combination regimen (TP/PD-L1) and failed. Methods　The elderly patients with NSCLC who who took TP/PD-L1 and failed at Nanyang Central Hospital from January 2019 to January 2022 were prospectively selected and divided into control a group (46 cases) and an experimental group (47 cases) by the random number table method. There were 20 males and 26 females in the control group; they were (68.50±0.81) years old. There were 22 males and 25 females in the experimental group; they were (68.97±0.77) years old. All the patients were given dexamethasone acetate tablets before formal salvage 1.0 mg/time, 2 times/day, for 3 days, and withdrawn; 500 ml 0.9% NaCl was infused as hydration treatment before the formal chemotherapy administration. The control group intravenously dripped docetaxel 80 mg/m² for more than 1 h, once a day, for 21 d; 21 d was set as a treatment cycle. In addition, the experimental group orally took antolini hydrochloride 0.15 mg·kg^-1 in the early morning, 1 time/d, and stopped 7 d after every 14 d; 21 d was set as a treatment cycle. Both groups were treated for 4 cycles and followed up 1 year. The clinical efficacies, peripheral blood CD4⁺/CD8⁺ T lymphocyte subpopulation distribution, and incidences of adverse drug reaction rates were compared between the two groups by t and χ² tests. The Kaplan-Meier survival curves were plotted at 1 year to compare the difference in progression-free survival between the two groups. Results　A total of 97 cases were screened for enrollment in this project, and 4 cases were withdrawn due to lost visit and initiative quitting, and a total of 93 cases were successfully enrolled, including 46 cases in the control group and 47 cases in the experimental group. After the treatment, the objective remission rates were 57.45% (27/47) and 34.78% (16/46) and the disease control rates were 78.72% (37/47) and 58.70% (27/46) in the experimental group and the control group, respectively, with statistical differences (both P<0.05). There were statistical differences in the CD4⁺, CD8⁺, and CD4⁺/CD8⁺ between the experimental group and the control group [(587.69±13.98)/μl vs. (369.06±10.85) /μl, (401.71±8.51)/μl vs. (477.71±9.53)/μl, and (1.49±0.04) vs. (0.79±0.03); all P<0.05]. The median progression-free survival times were 9.9 months [HR=1.493 (95%CI 0.837-2.664)] and 8.8 months [HR=1.120 (95%CI 0.622-2.017)] in the experimental group and the control group, respectively, with a statistical difference (P<0.05). The adverse reactions found in both groups included myelosuppression, fever, impaired gastrointestinal function, nausea, and skin allergy; the incidences of adverse drug reactions in the experimental group and the control group were 36.17% (17/47) and 34.78% (16/46), respectively, with no statistical difference (P>0.05). Conclusion　Antolini hydrochloride combined with docetaxel is clinically effective and safe in the treatment of elderly patients with NSCLC who take TP/PD-L1 targeted chemotherapy and fail, and can significantly improve the ratio of CD4+/CD8+ T lymphocyte subpopulations in peripheral blood and their median survival time.

Key words:

Non-small cell lung cancer, Antolini hydrochloride, Docetaxel, Elderly, Chemotherapy failure, Salvage therapy, Programmed cell death protein-1 ligand

摘要：

目的　探讨盐酸安罗替尼联合多西他赛对“紫杉醇、顺铂、替雷利珠单抗联合方案”（TP/PD-L1）治疗失败后非小细胞肺癌（NSCLC）老年患者的临床疗效及安全性影响。方法　前瞻性选取2019年1月至2022年1月于南阳市中心医院接受TP/PD-L1失败NSCLC老年患者，采用随机数字表法分为对照组［46例，男20例，女26例，年龄（68.50±0.81）岁］与对照组［47例，男22例，女25例，年龄（68.97±0.77）岁］，所有研究对象正式挽救前均给予醋酸地塞米松片（1.0 mg/次，2次/d，持续应用3 d撤除），正式化疗给药前均输注0.9%氯化钠500 ml作为水化治疗。对照组给予80 mg/m²多西他赛行挽救治疗，静脉给药持续静滴1 h以上，1次/d，以21 d为一个治疗周期。试验组在对照组的基础上联合安罗替尼（0.15 mg·kg^-1）清晨口服，1次/d，每使用14 d后停药7 d，设定每周期持续21 d。两组均持续治疗4个周期，随访1年。采用t检验、χ²检验比较两组实体瘤临床疗效、外周血T淋巴细胞亚群CD4⁺/CD8⁺比例及药物不良反应率。绘制1年期Kaplan-Meier生存曲线比较两组无进展生存期的差异。结果　共筛选入组97例，因失访、主动退出4例，共成功入组93例，其中对照组46例，试验组47例。治疗后，试验组和对照组的客观缓解率分别为57.45%（27/47）、34.78%（16/46），疾病控制率分别为78.72%（37/47）、58.70%（27/46），差异均有统计学意义（均P<0.05）。试验组与对照组CD4⁺分别为（587.69±13.98）/μl、（369.06±10.85）/μl，CD8⁺分别为（401.71±8.51）/μl、（477.71±9.53）/μl，CD4⁺/CD8⁺分别为（1.49±0.04）、（0.79±0.03），差异均有统计学意义（均P<0.05）。试验组与对照组中位无进展生存期分别为9.9个月［HR（95%CI）：1.493（0.837～2.664）］和8.8个月［HR（95%CI）：1.120（0.622～2.017）］，差异有统计学意义（P<0.05）。两组共发现不良反应有骨髓抑制、发热、胃肠功能受损、恶心及皮肤过敏，试验组及对照组的药物不良反应率分别为36.17%（17/47）、34.78%（16/46），差异无统计学意义（P>0.05）。结论　盐酸安罗替尼联合多西他赛治疗TP/PD-L1靶向化疗失败的NSCLC老年患者临床效果良好，安全性高，可显著提高外周血CD4⁺/CD8⁺ T淋巴细胞亚群比例及中位生存时间。

关键词:

非小细胞肺癌, 安罗替尼, 多西他赛, 老年, 化疗失败, 挽救治疗, 程序性细胞死亡蛋白-1配体

Bai Xiaohang, Chang Zhendong, Mu Yanyan.

Therapeutic effect of antolini hydrochloride combined with docetaxel for elderly patients with NSCLC who took TP/PDL1 targeted chemotherapy and failed [J]. International Medicine and Health Guidance News, 2023, 29(24): 3551-3556.

白小航常振东穆艳艳.

安罗替尼联合多西他赛治疗TP/PDL1靶向失败NSCLC老年患者的疗效分析 [J]. 国际医药卫生导报, 2023, 29(24): 3551-3556.

References

[1] Jasper K, Stiles B, McDonald F, et al. Practical management of oligometastatic non-small-cell lung cancer[J]. J Clin Oncol, 2022,40(6):635-641. DOI: 10. 1200/JCO.21.01719.
[2] 张爽,吴洪芬,董莹,等.2023年第1版NCCN小细胞肺癌临床实践指南解读[J].实用肿瘤杂志,2022,37(6):485-489.DOI:10.13267/j.cnki.syzlzz.2022.082.
[3] 王雷,李婧怡,李幸,等.晚期非小细胞肺癌免疫检查点抑制剂治疗专家共识解读[J].河北医科大学学报,2020,41(1):1-6,11.DOI:10.3969/j.issn.1007-3205.2020.01.001.
[4] 周彩存,王洁,王宝成,等.中国非小细胞肺癌免疫检查点抑制剂治疗专家共识(2020年版)[J].中国肺癌杂志,2021,24(4):217-235.DOI:10.3779/j.issn.1009-3419. 2021.101.13.
[5] Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer[J]. Nature, 2018,553(7689):446-454. DOI: 10.1038/nature25183.
[6] 马慧利,任中海,尚付梅,等.安罗替尼联合多西他赛二线治疗驱动基因阴性晚期非小细胞肺癌的疗效及安全性[J].实用癌症杂志,2023,38(3):476-480,484.DOI:10.3969/j.issn.1001-5930.2023.03.032.
[7] 中华医学会,中华医学会肿瘤学分会,中华医学会杂志社.中华医学会肺癌临床诊疗指南(2018版)[J].中华肿瘤杂志,2018,40(12):935-964.DOI:10.3760/cma.j.issn.0253- 3766. 2018.12.012.
[8] Seymour L, Bogaerts J, Perrone A, et al. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics[J]. Lancet Oncol, 2017,18(3):e143-e152. DOI: 10.1016/S1470-2045(17)30074-8.
[9] 吴爱菊,叶逢松,叶鸿,等.T淋巴细胞亚群评估晚期非小细胞肺癌放化疗后预后的价值[J].中国卫生检验杂志,2022,32(12):1494-1498.
[10] Antonia SJ, Borghaei H, Ramalingam SS, et al. Four-year survival with nivolumab in patients with previously treated advanced non-small-cell lung cancer: a pooled analysis[J]. Lancet Oncol, 2019,20(10):1395-1408. DOI: 10.1016/S1470-2045(19)30407-3.
[11] Dueck AC, Mendoza TR, Mitchell SA, et al. Validity and reliability of the US national cancer institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)[J]. JAMA Oncol, 2015,1(8):1051-1059. DOI: 10.1001/jamaoncol.2015.2639.
[12] 姚源山,华青旺,高文.晚期非小细胞肺癌患者免疫治疗的预后相关因素分析[J].实用肿瘤杂志,2023,38(3):239-245.DOI:10.13267/j.cnki.syzlzz.2023.037.
[13] 王硕,邓云天,彭欢,等.非小细胞肺癌免疫检查点抑制剂治疗进展[J].协和医学杂志,2023,14(2):409-415.DOI:10.12290/xhyxzz.2022-0151.
[14] 中国抗癌协会肿瘤病理专业委员会肺癌学组,中国抗癌协会肺癌专业委员会,PD-L检测共识专家组.非小细胞肺癌PD-L1免疫组织化学检测规范中国专家共识[J].中国肺癌杂志,2020,23(9):733-740.DOI:10.3779/j.issn.1009- 3419.2020.101.43.
[15] 赵论,张浩然,石默晗,等.安罗替尼联合多西他赛二线治疗无驱动基因晚期非小细胞肺癌的临床疗效观察[J].中华全科医学,2020,18(4):537-541.DOI:10.16766/j.cnki.issn. 1674-4152.001292.
[16] 王渊,谭盼,张靖.替雷利珠单抗联合PC方案治疗晚期肺癌的疗效及对血清PI3K、Akt的影响[J].中国医院用药评价与分析,2023,23(3):268-271.DOI:10.14009/j.issn.1672- 2124.2023.03.003.
[17] 李咏生,孙建国,李梦侠,重庆肺癌精准治疗协作组(CPLOG).第三代EGFR-TKI耐药后诊疗策略专家共识[J/CD].中华肺部疾病杂志(电子版),2023,16(2):145-155.DOI:10.3877/cma.j.issn.1674-6902.2023.02.001.
[18] Jia L, Gao X, Fang Y, et al. TM2, a novel semi-synthetic taxoid, exerts anti-MDR activity in NSCLC by inhibiting P-gp function and stabilizing microtubule polymerization[J]. Apoptosis, 2022,27(11-12):1015-1030. DOI: 10.1007/s10495-022-01767-4.
[19] 武春秋,张允清,张洪涛,等.安罗替尼联合多西他赛二线治疗广泛期小细胞肺癌的疗效和安全性[J].中华肿瘤防治杂志,2023,30(6):368-374.DOI:10.16073/j.cnki.cjcpt. 2023.06.08.
[20] 李家军,张腾跃.安罗替尼联合多西他赛三线治疗晚期肺鳞癌的临床研究[J].蚌埠医学院学报,2020,45(9):1220-1223,1227.DOI:10.13898/j.cnki.issn.1000-2200.2020.09.021.
[21] 裴书飞,张向东,卢万里.盐酸安罗替尼联合多西他赛治疗晚期食管癌的疗效及对血清肿瘤标志物和免疫功能的影响[J].中国临床医生杂志,2023,51(4):443-446.DOI:10.3969/j.issn.2095-8552.2023.04.019.
[22] 慈明伟,柯娇娇,张宁月.安罗替尼联合依托泊苷加顺铂治疗广泛期小细胞肺癌的临床观察[J].国际医药卫生导报,2022,28(20):2937-2940.DOI:10.3760/cma.j.issn.1007- 1245.2022.20.027.
[23] 惠燕红.多西他赛联合顺铂治疗老年晚期非小细胞肺癌的近期疗效及生存质量分析[J].淮海医药,2019,37(5):534-536.DOI:10.14126/j.cnki.1008-7044.2019.05.037.
[24] 中国医师协会肿瘤医师分会,中国临床肿瘤学会血管靶向治疗专家委员会,中国抗癌协会肿瘤靶向治疗专业委员会.盐酸安罗替尼治疗晚期肺癌中国专家共识(2020版)[J].中华肿瘤杂志,2020,42(10):807-816.DOI:10.3760/cma.j.cn112152-20200721-00669.
[25] 杨润梓,张语心,徐焕昌,等.安罗替尼联合多西他赛治疗晚期非小细胞肺癌的系统评价[J].医学研究杂志,2023,52(3):71-76.DOI:10.11969/j.issn.1673-548X.2023.03.016.
[26] 王伟,李鹏飞,马鹏飞,等.安罗替尼联合多西他赛治疗晚期非小细胞肺癌的近期疗效及对远期生存和不良反应的影响[J].癌症进展,2022,20(2):181-183.DOI:10.11877/j.issn.1672-1535.2022.20.02.20.
[27] 刘丽娅,朱颖,涂长玲,等.安罗替尼对比多西他赛用于一线治疗失败后晚期非小细胞肺癌的疗效及安全性研究[J].中国肿瘤外科杂志,2021,13(2):177-181.DOI:10.3969/j.issn.1674-4136.2021.02.015.
[28] 王李雪,王豪杰,欧阳伟炜,等.外周血CD4+T细胞水平及CD4+/CD8+比值对Ⅳ期非小细胞肺癌生存影响[J].中华放射肿瘤学杂志,2020,29(9):751-756.DOI:10.3760/cma.j.cn113030-20200329-00143.
[29] Duchemann B, Naigeon M, Auclin E, et al. CD8+PD-1+ to CD4+PD-1+ ratio (PERLS) is associated with prognosis of patients with advanced NSCLC treated with PD-(L)1 blockers[J]. J Immunother Cancer, 2022,10(2):e004012. DOI: 10.1136/jitc-2021-004012.
[30] Stankovic B, Bjørhovde HAK, Skarshaug R, et al. Immune cell composition in human non-small cell lung cancer[J]. Front Immunol, 2019,9:3101. DOI: 10.3389/fimmu.2018.03101.