奥沙利铂联合卡培他滨或联合替吉奥新辅助化疗方案在进展期胃癌治疗中的安全性和有效性

Safety and effectiveness of oxaliplatin combined with capecitabine or oxaliplatin combined with S-1 neoadjuvant chemotherapy in the treatment of advanced gastric cancer

目的探讨奥沙利铂联合卡培他滨(CapeOX)或奥沙利铂联合替吉奥(SOX)新辅助化疗方案在局部进展期胃癌治疗中的安全性和有效性。方法采用回顾性队列研究方法,收集2016年4月至2019年4月期间,于上海交通大学医学院附属瑞金医院予以新辅助化疗并接受标准腹腔镜下胃癌根治术的进展期胃癌患者的临床资料。病例纳入标准:(1)年龄≥18岁;(2)病理组织学确诊为胃腺癌,临床分期为T_(3-4)aN+M_(0);(3)肿瘤可切除;(4)术前接受CapeOX或SOX方案新辅助化疗,未接受过放疗及其他方案的化疗;(5)未合并其他恶性肿瘤;(6)美国东部肿瘤协作组(ECOG)评分≤1分;(7)无骨髓抑制;(8)肝、肾功能正常。排除标准:(1)胃癌复发患者;(2)因肿瘤穿孔、出血、梗阻等而行急诊手术的患者;(3)对奥沙利铂、替吉奥、卡培他滨及药物辅料过敏;(4)罹患冠心病、心肌病或美国纽约心脏病协会心功能分级Ⅲ-Ⅳ级;(5)妊娠或哺乳期妇女。共计118例患者入组(新辅助化疗组),纳入同期住院接受手术及术后辅助化疗的379例局部进展期胃癌患者作为辅助化疗组。依据性别、年龄、ECOG评分、肿瘤部位、临床分期、化疗方案等因素,采用倾向性评分匹配研究方法,将新辅助化疗组与辅助化疗组进行1∶1匹配后,两组各为40例。比较分析两组患者一般情况、新辅助化疗疗效、术中情况、术后情况、病理组织学结果、化疗相关不良事件、生存状况等方面的差异。结果两组患者匹配后的基线资料比较,差异无统计学意义(均P>0.05)。新辅助化疗组术前5.0%(2/40)达到完全缓解,57.5%(23/40)达到部分缓解,32.5%(13/40)达到疾病稳定,5.0%(2/40)疾病进展;客观缓解率为62.5%(25/40),疾病控制率95.0%(38/40)。新辅助化疗组与辅助化疗组患者手术时间、术中出血量、淋巴结清扫数目、术后住院天数和术后并发症发生率比较,差异均无统计学意义(均P>0.05)。新辅助化疗组手术相关并发症总发生率为12.5%(5/40),辅助化疗组为15.0%(6/40),两组比较,差异无统计学意义(χ^(2)=0.105,P=0.74),均经保守治疗后恢复;两组患者均未出现Clavien-Dindo Ⅳ或Ⅴ级并发症。术后病理结果提示,新辅助化疗组中病理分期T1的患者比例高于辅助化疗组[27.5%(11/40)比5.0%(2/40)],而病理分期T3的患者比例低于辅助化疗组[20.0%(8/40)比45.0%(18/40)],差异有统计学意义(χ^(2)=15.432,P=0.001)。新辅助化疗组肿瘤退缩分级:0级4例,1级8例,2级16例,3级12例,病理完全缓解率为10%(4/40),总体病理反应率为70.0%(28/40)。两组患者化疗相关不良事件发生率[40%(16/40)比37.5%(15/40)]比较,差异无统计学意义(P>0.05)。两组总生存期(43个月比40个月)和3年总体生存率(66.1%比59.8%)比较,差异无统计学意义(P=0.428);新辅助化疗组无病生存期和3年无病生存率均优于辅助化疗组(36个月比28个月,51.4%比35.8%,P=0.048)。结论 CapeOX或SOX新辅助化疗方案对于局部进展期胃癌患者具有较好的有效性和安全性,未增加手术风险,可改善患者的无病生存状况。

Objective To explore the safety and efficacy of oxaliplatin plus capecitabine(CapeOX)or oxaliplatin plus S-1(SOX)regimen neoadjuvant chemotherapy in the treatment of advanced gastric cancer.Methods A retrospective cohort study was performed.Clinical data of patients diagnosed as advanced gastric cancer undergoing CapeOX/SOX neoadjuvant chemotherapy and standard laparoscopic radical operation for gastric cancer in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from April 2016 to April 2019 were retrospectively collected.Inclusion criteria were as follows:(1)age≥18 years;(2)gastric adenocarcinoma was confirmed by histopathology and the clinical stage was T3-4aN+M0;(3)tumor could be resectable;(4)preoperative neoadjuvant chemotherapy was CapeOX or SOX regimen without radiotherapy or other regimen chemotherapy;(5)no other concurrent malignant tumor;(6)the Eastern Cooperative Oncology Group(ECOG)score≤1;(7)no bone marrow suppression;(8)normal liver and kidney function.Exclusion criteria were as follows:(1)patients with recurrent gastric cancer;(2)patients receiving emergency surgery due to tumor perforation,bleeding,obstruction,etc.;(3)allergy to oxaliplatin,S-1,capecitabine or any drug excipients;(4)diagnosed with coronary heart disease,cardiomyopathy,or the New York Heart Association class Ⅲ or Ⅳ;(5)pregnant or lactating women.A total of 118 patients were enrolled as the neoadjuvant chemotherapy group,and 379 patients with locally advanced gastric cancer who received surgery combined with postoperative adjuvant chemotherapy over the same period simultaneously were included as the adjuvant chemotherapy group.After propensity score matching was performed including gender,age,ECOG score,tumor site,clinical stage,chemotherapy regimen and other factors by 1:1 ratio,there were 40 cases in each group.The differences between the two groups in general conditions,efficacy of neoadjuvant chemotherapy,intraoperative conditions,postoperative conditions,histopathological results,chemotherapy-related adverse events,and survival status were compared and analyzed.Results Comparison of baseline demographics between the two groups showed no statistically significant difference(all P>0.05).In the neoadjuvant chemotherapy group,5.0%(2/40)of patients achieved clinical complete response,57.5%(23/40)achieved partial response,32.5%(13/40)remained stable disease,and 5.0%(2/40)had disease progression before surgery.Objective response rate was 62.5%(25/40),and disease control rate was 95.0%(38/40).There were no statistically significant differences between neoadjuvant chemotherapy group and adjuvant chemotherapy group in terms of operation time,intraoperative blood loss,number of lymph node harvested,length of postoperative hospital stay,and postoperative mortality and morbidity(all P>0.05).Postoperative complications were well managed with conservative treatment.No Clavien-Dindo Ⅳ or Ⅴ complications were observed in both groups.Pathological results showed that the proportion of patients with pathological stage T1 in the neoadjuvant chemotherapy group was significantly higher than that in the adjuvant chemotherapy group[27.5%(11/40)vs.5.0%(2/40)],while the proportion of patients with pathological stage T3 was significantly lower than that in the adjuvant chemotherapy group[20.0%(8/40)vs.45.0%(18/40)],with statistically significant difference(χ^(2)=15.432,P=0.001).In the neoadjuvant chemotherapy group,there were 4 cases of tumor regression grade 0,8 cases of grade 1,16 cases of grade 2,and 12 cases of grade 3.The pathological complete response rate was 10%(4/40),the overall pathological response rate was 70.0%(28/40).There was no statistically significant difference in the incidence of chemotherapy-related adverse events between neoadjuvant chemotherapy group and adjuvant chemotherapy group[40%(16/40)vs.37.5%(15/40),P>0.05].There were no statistically significant differences in OS(43 months vs.40 months)and 3-year OS rate(66.1%vs.59.8%)between neoadjuvant chemotherapy group and adjuvant chemotherapy group(P=0.428).The disease-free survival(DFS)and 3-year DFS rates of the neoadjuvant chemotherapy group were significantly superior to those of the adjuvant chemotherapy group(36 months vs.28 months,51.4%vs.35.8%,P=0.048).Conclusion CapeOX or SOX regimen neoadjuvant chemotherapy is a safe,effective and feasible treatment mode for advanced gastric cancer without increasing surgical risk and can improve the DFS of patients.