阿帕替尼联合奥沙利铂和替吉奥在胃癌腹膜转移转化治疗中的安全性及近期疗效观察

目的探讨阿帕替尼联合奥沙利铂和替吉奥在胃癌腹膜转移转化治疗中的安全性和近期疗效。方法回顾性分析"甲磺酸阿帕替尼联合替吉奥及奥沙利铂转化治疗晚期胃癌的单臂探索性临床研究"(中国临床试验注册号:ChiCTR-ONC-17010430)的前瞻性研究病例数据库,纳入18~70岁,经组织学及腹腔镜探查证实为胃癌腹膜转移,治疗前未接受放疗、化疗、靶向治疗或免疫治疗的患者。入组患者术前接受6个周期的替吉奥(80~120 mg/d,d1~14)和奥沙利铂(130 mg/m²,d1)以及5周期的阿帕替尼(500 mg/d,d1~21)转化方案治疗,化疗结束后3周,结合评估结果和患者意愿决定是否进行手术。主要观察指标为转化治疗的不良反应情况,次要观察指标为客观缓解率、疾病控制率和总体生存率(OS)。随访时间截至2020年5月。结果本研究共纳入胃癌腹膜转移患者27例,男性13例,女性14例,中位年龄为58岁(30~68岁),腹膜转移分型P1a 9例,P1b 5例,P1c 13例,腹膜癌指数(PCI)1~5分共14例,≥6分者13例。化疗不良反应的发生率为100%,最常见的血液学不良反应事件是白细胞减少(70.4%,19/27)和粒细胞减少(74.1%,20/27);非血液学不良反应事件为疲乏(51.9%,14/27)和口腔黏膜炎(37.0%,10/27);1例因4级血小板减少退组。26例可行疗效评估的患者中,18例(69.2%)获得部分缓解,3例(11.5%)获得疾病稳定,5例(19.2%)疾病进展,客观缓解率为69.2%(18/26),疾病控制率为80.8%(21/26)。14例患者接受手术,6例行R0切除,R0切除率42.9%(6/14)。术后病理反应率为64.3%(9/14)。随访时间12~40个月,随访率为100%。全组患者1年OS为65.2%,生存时间为(14.0±1.7)个月。P1a/P1b与P1c患者1年OS分别为81.8%与42.0%,差异有统计学意义(P=0.041)。PCI评分1~5分与≥6分的患者1年OS分别为67.3%与38.5%,差异有统计学意义(P=0.022)。结论在胃癌腹膜转移患者中,阿帕替尼联合奥沙利铂和替吉奥转化治疗方案的安全性可接受,且在P1a/P1b及PCI评分1~5分的患者中显示出良好的近期生存获益。

Safety and short-term efficacy of apatinib combined with oxaliplatin and S-1 in the conversion treatment for gastric cancer with peritoneal metastasis

Objective To investigate the safety and short-term efficacy of apatinib combined with oxaliplatin and S-1 in the conversion treatment for gastric cancer with different types of peritoneal metastasis.Methods A prospective study"one arm exploratory clinical study of conversion therapy of apatinib with S-1 and oxaliplatin in the treatment of advanced gastric cancer"(clinical registration ChiCTR-ONC-17010430)from medical record database was retrospectively analyzed.Patients aged 18-70 years with gastric cancer peritoneal metastasis confirmed by histology and laparoscopic exploration,and had not receive radiotherapy,chemotherapy,targeted therapy or immunotherapy before were enrolled.Before operation,the patients received 6 cycles of S-1(80-120 mg/d,d1-d14)and oxaliplatin(130 mg/m2,d1),and 5 cycles of apatinib(500 mg/d,d1-d21)conversion regimen.Three weeks after chemotherapy,whether the operation was performed or not depending on re-evaluation and patient preference.The main outcome were adverse reactions,and the secondary outcome were objective remission rate(ORR),disease control rate(DCR),and overall survival(OS)rate.The follow-up period was up to May 2020.Results A total of 27 patients with gastric cancer peritoneal metastasis were enrolled in this study.There were 13 males and 14 females,with a median age of 58(30-68)years old.There were 9 cases of P1a,5 cases of P1b,and 13 cases of P1c.There were 14 cases with 1-5 scores of PCI(peritoneal cancer index),and 13 cases with 6 scores or above.The incidence of adverse reactions was 100%.The most common adverse reactions were hematological events including leucopenia(70.4%,19/27)and granulocytopenia(74.1%,20/27).Non-hematological adverse events included fatigue(51.9%,14/27)and oral mucositis(37.0%,10/27).One patient was withdrawn due to grade 4 thrombocytopenia.Among 26 patients with feasible efficacy evaluation,18(69.2%)achieved partial remission,3(11.5%)achieved stable disease,and 5(19.2%)disease progression.The objective remission rate was 69.2%(18/26)and the disease control rate was 80.8%(21/26).Fourteen patients underwent surgery,including 6 patients undergoing R0 resection with the R0 resection rate of 42.9%(6/14).The postoperative pathological response rate was 64.3%(9/14).The follow-up time was 12-40 months,and the follow-up rate was 100%.The 1-year OS rate was 65.2%and the survival time was(14.0±1.7)months.The 1-year OS rates of P1a/P1b group and P1c group were 81.8%and 42.0%respectively,whose difference was statistically significant(P=0.041).The 1-year OS rates of PCI 1-5 group and PCI≥6 group were 67.3%and 38.5%respectively,whose difference was statistically significant(P=0.022).Conclusion In the conversion treatment of gastric cancer peritoneal metastasis,the safety of apatinib combined with oxaliplatin and S-1 is acceptable,and this regimen shows a good short-term survival efficacy in patients with P1a/P1b and PCI of 1-5.