吉非替尼联合顺铂治疗晚期非小细胞肺癌的临床研究

Clinical study of gefitinib combine with cisplatin in treatment of advanced non-small cell lung cancer

目的回顾性分析吉非替尼联合顺铂治疗晚期非小细胞肺癌的临床疗效。方法选取2017年2月-2020年4月淮南东方医院集团总医院收治的60例晚期非小细胞肺癌,根据用药方案不同分为对照组和治疗组,每组各30例。对照组化疗第1天静脉滴注注射用培美曲塞二钠,500 mg/m^(2),注射时间大于10 min,化疗第1~3天静脉滴注顺铂注射液,75 mg/m^(2),给药前2~16 h和给药后至少6 h内必需进行充分的水化治疗。治疗组从化疗第1天开始口服吉非替尼片,250 mg/d,同时化疗第1~3天静脉滴注顺铂注射液,用法用量同对照组。两组均以3周为1个疗程,治疗2个疗程。观察两组的临床疗效,比较两组治疗前后生活质量相关评分、免疫功能指标、肿瘤标志物、血清细胞因子水平的变化情况。结果治疗后,治疗组客观缓解率(ORR)、疾病控制率(DCR)分别是60.0%、90.0%,显著高于对照组的33.3%、70.0%(P<0.01)。治疗后,对照组躯体、心理、社会、总分均显著低于治疗前(P<0.05),两组KPS评分显著高于治疗前(P<0.05);治疗后治疗组患者躯体、心理、社会、总分及KPS评分均显著高于对照组(P<0.05)。治疗后,治疗组CD4^(+)和CD4^(+)/CD8^(+)均显著上升,CD8^(+)下降(P<0.05);对照组CD4^(+)和CD4^(+)/CD8^(+)均显著下降(P<0.05),CD8^(+)有上升趋势但无统计学意义。治疗后,治疗组患者CD4^(+)和CD4^(+)/CD8^(+)显著高于对照组,CD8^(+)低于对照组(P<0.05)。治疗后,两组癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)、血管内皮生长因子(VEGF)均显著下降(P<0.05);且治疗后治疗组CEA、NSE、VEGF水平显著低于对照组(P<0.05)。治疗后,两组患者白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、干扰素-γ(INF-γ)显著升高,而白细胞介素-4(IL-4)显著降低(P<0.01);且治疗后,治疗组IL-6和INF-γ显著高于对照组(P<0.05)。随访发现,治疗组总生存率(OS)、无进展生存率(PFS)中位生存时间分别为20.6、28个月,对照组为16、19个月。Log-rank(Mantel-Cox)test结果显示,治疗组PFS显著优于对照组(P<0.05),而OS虽有一定趋势但无显著性差异。结论吉非替尼联合顺铂可有效治疗晚期非小细胞肺癌患者,提高ORR、DCR,改善患者携瘤生活质量,提高无进展生存率,且无显著不良反应。

Objective The clinical efficacy of gefitinib combined with cisplatin in treatment of advanced non-small cell lung cancer was retrospectively analyzed.Methods Patients(60 cases)with advanced non-small cell lung cancer admitted to Huainan Oriental Hospital Group General Hospital from February 2017 to April 2020 were selected and divided into control and treatment group according to different medication regimen,with 30 cases in each group.Patients in the control group were iv administered with Pemetrexed Disodium for injection,500 mg/m^(2),the injection time is longer than 10 min,and on the 1st to 3rd day of chemotherapy,they were iv administered with Cisplatin Injection,75 mg/m^(2),and adequate hydration treatment is necessary for 2 to 16 h before and at least 6 h after administration.Patients in the treatment group were po administered with Gefitinib Tablets,250 mg/d.And on the 1st to 3rd day of chemotherapy,Cisplatin Injection was injected intravenously with the same dosage as the control group.3 Weeks was as 1 course,and two groups were treated for 2 courses.The clinical effects of the two groups were observed,and the changes of quality-of-life scores,immune function indexes,tumor markers and serum cytokine levels before and after treatment were compared between the two groups.Results After treatment,the objective response rate(ORR)and disease control rate(DCR)in the treatment group were 60.0%and 90.0%,respectively,which were significantly higher than those in the control group(33.3%and 70.0%,P<0.05).After treatment,the physical,psychological,social,and total score of the control group were significantly lower than before treatment(P<0.05),and the Cassiar score of the two groups were significantly higher than before treatment(P<0.05).After treatment,the physical,psychological,social,total score and Carlisle score of the treatment group were significantly higher than those of the control group(P<0.05).After treatment,CD4^(+)and CD4^(+)/CD8^(+)in treatment group were significantly increased,while CD8^(+)was decreased(P<0.05).In the control group,CD4^(+)and CD4^(+)/CD8^(+)were significantly decreased(P<0.05),while CD8^(+)showed an upward trend without statistical significance.After treatment,CD4^(+)and CD4^(+)/CD8^(+)in treatment group were significantly higher than those in control group,and CD8^(+)was lower than those in control group(P<0.05).After treatment,CEA,NSE and VEGF were significantly decreased in both groups(P<0.05).After treatment,the levels of carcinoembryonic antigen(CEA),neuron-specific enolase(NSE)and vascular endothelial growth factor(VEGF)in treatment group were significantly lower than those in control group(P<0.05).After treatment,interleukin-2(IL-2),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and interferon-γ(INF-γ)were significantly increased in both groups,while interleukin-4(IL-4)was significantly decreased(P<0.01).After treatment,IL-6 and INF-γin the treatment group were significantly higher than those in the control group(P<0.05).The median survival time of overall survival(OS)and progression-free survival(PFS)was 20.6 and 28 months in the treatment group and 16 and 19 months in the control group,respectively.Log-rank(Mantel-Cox)test results showed that PFS in the treatment group was significantly better than that in the control group(P<0.05),while OS had a certain trend but no significant difference.Conclusion Gefitinib combine with cisplatin can effectively treat advanced non-small cell lung cancer,and can improve ORR,DCR,the quality of life and progression-free survival rate,which was no significant adverse reactions.