复发转移食管鳞状细胞癌治疗进展

摘要/Abstract

摘要：

复发转移食管鳞状细胞癌(ESCC)预后差,治疗选择有限。以铂类为基础联合氟尿嘧啶或紫杉醇类的化疗为其标准一线治疗方案。以西妥昔单抗、帕尼单抗、尼妥珠单抗和吉非替尼等表皮生长因子受体抑制剂为主的分子靶向治疗药物,均未能改善晚期ESCC患者的生存。多靶点小分子酪氨酸激酶抑制剂安罗替尼应用于二线以上治疗可延长患者的中位无进展生存期。相较于化疗,免疫检查点抑制剂(如纳武利尤单抗、帕博利珠单抗、卡瑞利珠单抗)可显著延长一线化疗失败ESCC患者的总生存期,可作为标准二线治疗的选择。免疫治疗联合化疗或抗血管生成治疗应用于晚期ESCC一线治疗的研究也正在进行中。

关键词:食管肿瘤,复发,肿瘤转移,药物疗法

Abstract:

Relapse or metastatic esophageal squamous cell carcinoma (ESCC) has poor prognosis and limited treatment options. Chemotherapy based on platinum agents combined with fluorouracil or taxanes is the standard first-line treatment for it. Molecular-targeting agents, mainly epidermal growth factor receptor inhibitors including cetuximab, panitumumab, nimotuzumab and gefitinib, have failed to improve the survival of patients with advanced ESCC. Anlotinib, one of the small molecule multi-target tyrosine kinase inhibitors, can prolong the median progression free survival in patients treated with above the second line. Compared with chemotherapy, immune checkpoint inhibitors (including nivolumab, pembrolizumab and camrelizumab) significant improve overall survival times in patients with ESCC who fail to the first line chemotherapy, and can be selected as the standard second line treatment. Immunotherapy combined with chemotherapy or anti-angiogenic therapy for first-line treatment of advanced ESCC is also being studied.

Key words:Esophageal neoplasms,Recurrence,Neoplasm metastasis,Drug therapy

池秀盈, 王鸿彪, 李植锋, 林英城. 复发转移食管鳞状细胞癌治疗进展[J]. 国际肿瘤学杂志, 2021, 48(12): 755-759.

Chi Xiuying, Wang Hongbiao, Li Zhifeng, Lin Yingcheng. Progression in the therapies of relapse or metastatic esophageal squamous cell carcinoma[J]. Journal of International Oncology, 2021, 48(12): 755-759.

参考文献23

[1]	Lee S, Cohen DJ. Pharmacotherapy for metastatic esophageal cancer: where do we need to improve?[J]. Expert Opin Pharmacother, 2019,20(3):357-366. DOI: 10.1080/14656566.2018.1551881.
[2]	Huang J, Xu B, Liu Y, et al. Irinotecan plus S-1 versus S-1 in patients with previously treated recurrent or metastatic esophageal cancer (ESWN 01): a prospective randomized, multicenter, open-labeled phase 3 trial[J]. Cancer Commun (Lond), 2019,39(1):16. DOI: 10.1186/s40880-019-0359-7.
[3]	Huang ZH, Ma XW, Zhang J, et al. Cetuximab for esophageal cancer: an updated meta-analysis of randomized controlled trials[J]. BMC Cancer, 2018,18(1):1170. DOI: 10.1186/s12885-018-5040-z.
[4]	Moehler M, Maderer A, Thuss-Patience PC, et al. Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase ⅢAIO/EORTC trial (POWER)[J]. Ann Oncol, 2020,31(2):228-235. DOI: 10.1016/j.annonc.2019.10.018.
[5]	Dutton SJ, Ferry DR, Blazeby JM, et al. Gefitinib for oesophageal cancer progressing after chemotherapy (COG): a phase 3, multi-centre, double-blind, placebo-controlled randomised trial[J]. Lancet Oncol, 2014,15(8):894-904. DOI: 10.1016/S1470-2045(14)70024-5.
[6]	Zhang X, Jia J, Lu M, et al. Nimotuzumab plus paclitaxel and cisplatin as a 1st-line treatment for esophageal cancer: long term follow-up of a phase Ⅱ study[J]. J Cancer, 2019,10(6):1409-1416. DOI: 10.7150/jca.28659.
[7]	Matsuoka T, Yashiro M. Molecular-targeted therapy toward precision medicine for gastrointestinal caner: current progress and challenges[J]. World J Gastrointest Oncol, 2021,13(5):366-390. DOI: 10.4251/wjgo.v13.i5.366.
[8]	Huang J, Xiao J, Fang W, et al. Anlotinib for previously treated advanced or metastatic esophageal squamous cell carcinoma: a double-blind randomized phase 2 trial[J]. Cancer Med, 2021,10(5):1681-1689. DOI: 10.1002/cam4.3771.
[9]	Li J, Jia Y, Gao Y, et al. Clinical efficacy and survival analysis of apatinib combined with docetaxel in advanced esophageal cancer[J]. Onco Targets Ther, 2019,12:2577-2583. DOI: 10.2147/OTT.S191736.
[10]	Kudo T, Hamamoto Y, Kato K, et al. Nivolumab treatment for oesophageal squamous-cell carcinoma: an open-label, multicentre, phase 2 trial[J]. Lancet Oncol, 2017,18(5):631-639. DOI: 10.1016/S1470-2045(17)30181-X.
[11]	Kato K, Cho BC, Takahashi M, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial[J]. Lancet Oncol, 2019,20(11):1506-1517. DOI: 10.1016/S1470-2045(19)30626-6.
[12]	Chau I, Doki Y, Ajani JA, et al. Nivolumab (NIVO) plus ipilimumab (IPI) or NIVO plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): first results of the CheckMate 648 study[J]. J Clin Oncol, 2021,39(18 suppl). DOI: 10.1200/JCO.2021.39.15_suppl.LBA4001.
[13]	Doi T, Piha-Paul SA, Jalal SI, et al. Safety and antitumor activity of the anti-programmed death-1 antibody Pembrolizumab in patients with advanced esophageal carcinoma[J]. J Clin Oncol, 2018,36(1):61-67. DOI: 10.1200/JCO.2017.74.9846.
[14]	Shah MA, Kojima T, Hochhauser D, et al. Efficacy and safety of pembrolizumab for heavily pretreated patients with advanced, metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: the phase 2 KEYNOTE-180 study[J]. JAMA Oncol, 2019,5(4):546-550. DOI: 10.1001/jamaoncol.2018.5441.
[15]	Kojima T, Shah MA, Muro K, et al. Randomized phase Ⅲ KEYNOTE-181 study of pembrolizumab versus chemotherapy in advanced esophageal cancer[J]. J Clin Oncol, 2020,38(35):4138-4148. DOI: 10.1200/JCO.20.01888.
[16]	Chen J, Luo S, Qin S, et al. Pembrolizumab versus chemotherapy in patients with advanced/metastatic adenocarcinoma or squamous cell carcinoma of the esophagus as second line therapy: analysis of the Chinese subgroup in KEYNOTE-181[J]. Ann Oncol, 2019,30(5suppl):v294. DOI: 10.1093/annonc/mdz247.086.
[17]	Sun JM, Shen L, Shah MA, et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study[J]. Lancet, 2021,398(10302):759-771. DOI: 10.1016/S0140-6736(21)01234-4.
[18]	Hong Y, Ding ZY. PD-1 inhibitors in the advanced esophageal cancer[J]. Front Pharmacol, 2019,10:1418. DOI: 10.3389/fphar.2019.01418.
[19]	Huang J, Xu B, Mo H, et al. Safe, activity, and biomarkers of SHR-1210, an anti-PD-1 antibody, for patients with advanced esophageal carcinoma[J]. Clin Cancer Res, 2018,24(6):1296-1304. DOI: 10.1158/1078-0432.CCR-17-2439.
[20]	Huang J, Xu J, Chen Y, et al. Camrelizumab versus investigator's choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study[J]. Lancet Oncol, 2020,21(6):832-842. DOI: 10.1016/S1470-2045(20)30110-8.
[21]	Wang F, Ren C, Zhao Q, et al. Association of frequent amplification of chromosome 11q13 in esophageal squamous cell cancer with clinical benefit to immune check point blockade[J]. J Clin Oncol, 2019,37(35 suppl):4036-4036. DOI: 10.1200/JCO.2019.37.15_suppl.4036.
[22]	Xu RH, Wang F, Cui C, et al. A randomized, double-blind, phase Ⅲ study of toripalimab versus placebo in combination with first-line chemotherapy for treatment naive advanced or metastatic esophageal squamous cell carcinoma (ESCC)[J]. Ann Oncol, 2021,32:S1041. DOI: 10.1016/j.annonc.2021.08.1482.
[23]	Zhang B, Qi L, Wang X, et al. Phase Ⅱ clinical trial using camrelizumab combined with apatinib and chemotherapy as the first-line treatment of advanced esophageal squamous cell carcinoma[J]. Cancer Commun (Lond), 2020,40(12):711-720. DOI: 10.1002/cac2.12119.