厄洛替尼与培美曲塞加顺铂方案新辅助治疗ⅢA期表皮生长因子受体突变型肺腺癌的随机对照研究

A randomized controlled study of erlotinib versus pemetrexed combined with cisplatin in neoadjuvant therapy of stage ⅢA EGFR-mutant lung adenocarcinoma

目的评价表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）用于新辅助治疗的可行性、疗效和安全性。方法将86例ⅢA期EGFR突变型肺腺癌患者按随机数表法分为2组，新辅助靶向治疗组和新辅助化疗组各43例。新辅助靶向治疗组口服厄洛替尼，150 mg/次，1次/d，治疗9周。新辅助化疗组采用PP方案（培美曲塞＋顺铂），化疗2周期后休息3周。两组患者根据影像学检查评价疗效后行手术治疗。结果新辅助靶向治疗组完全缓解（CR） 4例，部分缓解（PR） 25例，缓解率为67.4%。组织学有效性评价Ⅰ级8例，Ⅱ级20例，组织学有效率为65.1%。毒副反应主要为皮疹、腹泻。新辅助化疗组CR 2例，PR 17例，缓解率为44.2%。组织学有效性评价Ⅰ级3例，Ⅱ级15例，组织学有效率为41.9%。毒副反应主要为血液学毒性。两组在缓解率、组织学有效性及血液学毒性方面，差异均有统计学意义（均P〈0.05）。新辅助靶向治疗组切除率为90.7%，术中失血（299.8±23.4）ml，拔除胸引管时间为（5.2±0.4）d，并发症发生率为9.3%；新辅助化疗组切除率为83.7%，术中失血（308.9±22.7）ml，拔除胸引流管时间为（5.4±0.6）d，并发症发生率为11.6%，两组差异均无统计学意义（均P〉0.05）。结论新辅助靶向治疗对ⅢA期EGFR突变型肺腺癌疗效确切，毒副反应轻，可作为ⅢA期EGFR突变型肺腺癌新辅助治疗的选择。

ObjectiveTo evaluate the feasibility, efficacy and safety of epidermal growth factor receptor-tyrosine kinase inhibitors（EGFR-TKIs） for neoadjuvant therapy.MethodsEighty-six patients with stage ⅢA EGFR-mutant lung adenocarcinoma were assigned to 2 groups （n=43 in each group） according to the random number table method： neoadjuvant targeted therapy group （single oral dose of erlotinib 150 mg per day, for 9 weeks） and neoadjuvant chemotherapy group （2 cycles of pemetrexed combined with cisplatin chemotherapy followed by 3- week discontinuation）. Surgical treatment was underwent after imaging efficacy evaluation.ResultsIn neoadjuvant targeted therapy group, 4 achieved complete response （CR）, 25 achieved partial response （PR）, giving an objective response rate （ORR） of 67.4%. In pathological response, 8 patients had grade Ⅰ, 20 patients had grade Ⅱ, giving a pathological response rate of 65.1%. The most frequent adverse events （AEs） were rash and diarrhea. In neoadjuvant chemotherapy group, 2 had CR and 17 had PR, giving an ORR of 44.2%. In pathological response, 3 patients had grade Ⅰ, 15 patients had grade Ⅱ, giving a pathological response rate of 41.9%. The main AEs were hematologic toxic effects. The ORR, histological efficacy and hematologic toxicity showed statistical significance between the two groups （P〈0.05）. The neoadjuvant targeted therapy group had 90.7% resection rate, （299.8±23.4） ml of hemorrhage volume during operation, （5.2±0.4） days of extubation time and 9.3% postoperative complication rate. Corresponding results were 83.7%, （308.9±22.7） ml, （5.4±0.6） days and 11.6% in neoadjuvant chemotherapy group, which showed no statistical significance （P〉0.05）.ConclusionsNeoadjuvant targeted treatment for stage ⅢA lung adenocarcinoma harboring EGFR mutations. The regimen could be considered as a choice of neoadjuvant treatment for patients with stage ⅢA EGFR-mutant lung adenocarcinoma.