吉非替尼联合恩度对比吉非替尼单药一线治疗EGFR突变阳性晚期肺腺癌的临床观察

Clinical observation of gefitinib combined with Endostar in the first-line treatment of EGFR mutation positive advanced lung adenocarcinoma

摘要:

目的： 探讨吉非替尼联合恩度对比吉非替尼单药一线治疗EGFR突变阳性晚期肺腺癌的临床疗效和不良反应。方法： 以成都市第五人民医院2016年1月至2019年1月收治的60例EGFR 19~21号外显子突变、不能手术或术后复发转移的肺腺癌患者为研究对象，随机分为对照组和研究组，每组30例，对照组患者使用单药吉非替尼口服治疗，研究组在此基础上联合恩度微泵治疗，21 d为1个周期。比较2组患者的客观有效率（objective response rate，ORR）、疼痛反应、肿瘤标志物、药物不良反应、无进展生存期（progression free survival，PFS）以及总体生存期（overall survival，OS）。结果： 研究组患者ORR明显高于对照组（83.33%vs.50.00%），具有统计学差异（P<0.05）。研究组疼痛缓解程度优于对照组，2组比较有统计学差异（P<0.05）。2组患者治疗后血清CEA、CYFRA21-1及CA199水平均降低，研究组下降程度优于对照组，差异有统计学意义（P<0.05）。2组患者均未出现IV级不良反应，研究组患者皮疹少于对照组，但有个别轻度出血的情况。对照组中位PFS为9.18个月（95%CI=7.80~10.56），研究组中位PFS为15.23个月（95%CI=13.07~17.39），差异有统计学意义（P<0.05）。对照组中位OS为17.98个月（95%CI=14.40~21.57），研究组中位OS为25.95个月（95%CI=20.09~26.17），差异有统计学意义（P<0.05）。进一步亚组分析显示，无论是19外显子还是21外显子突变的患者，研究组的PFS、OS较对照组均明显延长。结论： 吉非替尼与恩度联合一线治疗EGFR突变阳性晚期肺腺癌，可有效提高临床疗效，延长患者生存期，降低相关肿瘤标志物水平，同时不会增加药物不良反应率，其安全性较高，值得在晚期非小细胞肺癌的一线治疗中推广。

Abstract:

Objective: To investigate the clinical efficacy and adverse reactions of gefitinib combined with Endostar in the first-line treatment of EGFR mutation positive advanced lung adenocarcinoma. Methods: Sixty patients with lung adenocarcinoma with EGFR exon 19-21 mutation inoperability or postoperative recurrence and metastasis admitted to the Chengdu Fifth People's Hospital from January 2016 to January 2019 were randomized into control group and study group, with 30 cases in each group. Patients in control group were treated with gefitinib alone, while patients in study group were treated with Endostar on the basis of gefitinib, with 21 days as a cycle. Objective response rate (ORR), pain response, tumor markers, adverse drug reactions, progression free survival (PFS) and overall survival (OS) were compared between the two groups. Results: The ORR of the study group was significantly higher than that of the control group (83.33% vs.50.00%, P<0.05). The pain relief degree of the study group was significantly better than that of the control group (P<0.05). The level of tumor markers (serum CEA, CYFRA21-1 and CA199) in the two groups decreased after the treatment, and the study group dropped more significantly than the control group (P<0.05). There were no gradeⅣadverse reactions in both groups. The rash in the study group was less than that in the control group, but there were individual cases of mild bleeding. The mPFS of the control group was 9.18 months (95%CI=7.80-10.56), and the mPFS of the study group was 15.23 months (95%CI=13.07-17.39), with significant differences (P<0.05). The mOS of the control group was 17.98 months (95%CI=14.40-21.57) and that of the study group was 25.95 months (95%CI=20.09-26.17), with significant differences (P<0.05).Further subgroup analysis showed that PFS and OS in the study group were significantly longer than those in the control group, regardless of the mutation in exon 19 or exon 21. Conclusion: Gefitinib combined with Endostar in the first-line treatment of EGFR mutation positive advanced lung adenocarcinoma can effectively improve the clinical efficacy, prolong the survival period of patients, reduce the level of tumor markers, and does not increase the adverse drug reaction rate, with high security, which is worthy of promotion in the first-line treatment of advanced non-small cell lung cancer.