晚期食管鳞癌一线化疗失败后的治疗现状与问题

Current progress of the study on esophageal squamous carcinoma patients whose disease progresses after first-line chemotherapy

晚期食管鳞癌预后差,一线化疗失败后无标准治疗方案,需要寻找有效的新药。本文主要介绍了晚期食管鳞癌一线化疗失败后的化疗和靶向治疗及存在的问题,分别从单药化疗、联合化疗和靶向治疗3方面进行总结。针对食管鳞癌单药化疗的研究局限于回顾性分析,且疗效有限;联合化疗方案多以多西他赛或伊立替康为基础,多为小样本的临床研究,其报道有效率达11%-39%,值得进一步探索。靶向药物表皮生长因子受体-酪氨酸酶抑制剂（epidermal growth factor receptor-tyrosine kinase inhibitor,EGFRTKI）在食管鳞癌的二线治疗中已经有大型Ⅲ期临床研究的结果发表,结果显示吉非替尼在食管癌非选择人群中并不能改善生存。但一项Ⅱ期临床研究发现埃克替尼在部分选择人群的二线治疗中有效率为16.7%,提示寻找药物治疗的有效人群可能是提高药物治疗疗效的关键,或为未来食管癌二线治疗的主要研究方向。抗程序性死亡因子-1（programmed death 1,PD-1）抗体在晚期食管癌PD-L1基因阳性选择人群的二线治疗中具有突出的疗效和较好的安全性,免疫治疗的应用很可能会开启食管癌二线治疗的新途径。

Advanced esophageal squamous cell carcinoma（ESCC） has poor prognosis. No standard therapies have been established,and there are few treatment options available for these esophageal squamous carcinoma patients whose disease progresses after chemotherapy; thus,new agents are urgently needed. In this review,we summarized current second-line chemotherapy and targeted therapy and existing problems in the drug therapies for esophageal squamous carcinoma patients who failed in first-line chemotherapy from three aspects. Second-line single-agent chemotherapy for ESCC has shown limited efficacy according to relevant retrospective studies. Although combined chemotherapy based on docetaxel or irinotecan has been explored restrictively in relative small sample sizes,the reported ORR 11% - 39% was encouraging,suggesting the necessity of further exploration. A phase III study had illustrated that EGFR-TKI gefitinib as a second-line treatment for esophageal cancer in unselected patients does not improve overall survival. A phase II study showed favorable activity of icotinib as second-line therapy for ESCC patients with EGFR overexpression or amplification,of which ORR was 16. 7%. In conclusion, future research should focus on validation of predictive biomarkers to identify the responsive subgroup of patients. Furthermore,PD-1 antibody had been demonstrated by recent study of promising efficacy and favorable safety in the second-line treatment of PD-L1 gene-positive advanced esophageal cancer patients. Immunotherapy is believed to result in modifications in the treatment paradigm for esophageal cancer in the near future.