Mao Chengyi, Zeng Xiaoxi, Zhang Chao, Yang Yushang, Xiao Xin, Luan Siyuan, Zhang Yonggang, Yuan Yong
Department of Thoracic Surgery West China Hospital, Sichuan University, Chengdu, China.
West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China.
Front Cell Dev Biol. 2021 Feb 11;9:612451. doi: 10.3389/fcell.2021.612451. eCollection 2021.
Pharmaceutical therapies are essential for esophageal cancer (EC). For the advanced EC, the neoadjuvant therapy regimen, including chemotherapy plus radiotherapy and/or immunotherapy, is effective to achieve clinical benefit, even pathological complete response. For the unresectable, recurrent, and metastatic EC, the pharmaceutical therapy is the limited effective regimen to alleviate the disease and prolong the progression-free survival and overall survival. In this review, we focus on the pharmaceutical applications in EC treatment including cytotoxic agents, molecular targeted antibodies, and immune checkpoint inhibitors (ICIs). The chemotherapy regimen is based on cytotoxic agents such as platinum-based complexes, fluorinated pyrimidines and taxenes. Although the cytotoxic agents have been developed in past decades, the standard chemotherapy regimen is still the cisplatin and 5-FU or paclitaxel because the derived drugs have no significant advantages of overcoming the shortcomings of side effects and drug resistance. The targeted molecular therapy is an essential supplement for chemotherapy; however, there are only a few targeted therapies available in clinical practice. Trastuzumab and ramucirumab are the only two molecular therapy drugs which are approved by the US Food and Drug Administration to treat advanced and/or metastatic EC. Although the targeted therapy usually achieves effective benefits in the early stage therapy of EC, the patients will always develop drug resistance during treatment. ICIs have had a significant impact on routine clinical practice in cancer treatment. The anti-programmed cell death-1 monoclonal antibodies pembrolizumab and nivolumab, as the ICIs, are recommended for advanced EC by several clinical trials. However, the significant issues of pharmaceutical treatment are still the dose-limiting side effects and primary or secondary drug resistance. These defects of pharmaceutical therapy restrain the clinical application and diminish the effectiveness of treatment.
药物治疗对食管癌（EC）至关重要。对于晚期食管癌，新辅助治疗方案，包括化疗加放疗和/或免疫治疗，对于实现临床获益甚至病理完全缓解是有效的。对于不可切除、复发和转移性食管癌，药物治疗是缓解疾病、延长无进展生存期和总生存期的有限有效方案。在本综述中，我们重点关注药物在食管癌治疗中的应用，包括细胞毒性药物、分子靶向抗体和免疫检查点抑制剂（ICIs）。化疗方案基于细胞毒性药物，如铂类复合物、氟嘧啶和紫杉烷。尽管在过去几十年中已经开发了细胞毒性药物，但标准化疗方案仍然是顺铂和5-氟尿嘧啶或紫杉醇，因为衍生药物在克服副作用和耐药性缺点方面没有显著优势。靶向分子治疗是化疗的重要补充；然而，临床实践中可用的靶向治疗很少。曲妥珠单抗和雷莫西尤单抗是仅有的两种被美国食品药品监督管理局批准用于治疗晚期和/或转移性食管癌的分子治疗药物。尽管靶向治疗通常在食管癌的早期治疗中取得有效获益，但患者在治疗过程中总会产生耐药性。免疫检查点抑制剂对癌症治疗的常规临床实践产生了重大影响。抗程序性细胞死亡蛋白1单克隆抗体帕博利珠单抗和纳武利尤单抗作为免疫检查点抑制剂，在多项临床试验中被推荐用于晚期食管癌。然而，药物治疗的重大问题仍然是剂量限制性副作用以及原发性或继发性耐药。药物治疗的这些缺陷限制了其临床应用并降低了治疗效果。
