Ⅲ期非小细胞肺癌非手术治疗的现状与研究进展

Current Standards and Research Progress in Non-surgical Treatment for NSCLC Stage Ⅲ

肺癌是全球范围内引起肿瘤相关性死亡的主要原因,而肺癌中约85%为非小细胞肺癌(NSCLC)。Ⅲ期NSCLC患者是一复杂的人群,其中部分患者是可以治愈的。NSCLC的治疗包括手术、放疗、化疗以及靶向药物治疗,并且绝大多数身体合适患者接受的是化疗和放疗。Ⅲ期NSCLC患者的最佳治疗方案仍未统一,但一些治疗原则已被普遍接受。对身体状态良好、各器官功能正常的患者,同步放化疗是标准的治疗方案。常与放疗联合应用于肺癌治疗的化疗方案包括顺铂/依托泊苷方案和卡铂/紫杉醇方案。与传统方案相比,新药联合放疗并未提高治疗疗效。而关于诱导化疗、巩固化疗何种方式与放疗配伍更利于患者生存,仍然存在争议,迄今为止,Ⅲ期临床研究并未给出确切的结论。部分研究显示抗血管治疗与放化疗联合疗效不显著或存在危险。在未筛选Ⅲ期患者中,靶向治疗的疗效欠佳。尽管存在这些困难,但经选择的患者采用放化疗基础上加用分子靶向药物治疗或者在放化疗后加用免疫巩固治疗方案是可取的。本文将总结关于Ⅲ期NSCLC患者现有治疗手段和以表皮生长因子受体(EGFR)、间变性淋巴瘤激酶(ALK)、RAS、程序性死亡分子1(PD-1)及程序性死亡分子1配体(PD-L1)为靶点的药物相关研究。

Lung cancer is the leading cause of cancer throughout the world,of which non-small cell lung cancer（NSCLC） accounts for 85%. Patients with stage Ⅲ NSCLC is a heterogeneous group and some of them may be curable. Combinations of various therapeutic approaches including surgery,radiotherapy,chemotherapy and molecular targeted therapy are performed to treat this disease,and the majority of fit patients will be treated with chemotherapy and radiation alone. The optimal therapy for all patients remains undefined,but certain principles of care are widely accepted. Concurrent chemoradiation is the standard of care for patients who have a good performance status and adequate end-organ function. The most commonly used chemotherapy regimens given in combination with radiation therapy include cisplatin/etoposide or carboplatin/paclitaxel.Compared to these older regimens,studies incorporating newer agents have not improved outcomes. Whether the induction or consolidation chemotherapy following chemoradiation contribute to the survival or not is controversial,and thus far randomized phase Ⅲ trials have not provided supporting evidence for this strategy. There are some cases suggesting that incorporating antiangiogenics with chemoradiation may been ineffective or unsafe. Targeted agents in unselected patient diagnosed with stage Ⅲ disease have not shown survival favour. Despite these recent setbacks,however,there remains a sound rationale for incorporating molecularly targeted agents into chemoradiation regimens in select patient groups or consolidating chemoradiation with immunotherapy. Current standards and clinical trials that incorporate drugs targeting EGFR,ALK,RAS,programmed cell death 1（PD-1） and programmed death ligand 1（PD-L1） into the management of patients with stage Ⅲ NSCLC are reviewed.