腹腔热灌注紫杉醇联合阿帕替尼、替吉奥化疗对单纯脱落细胞学阳性胃癌患者转化治疗效果

Effect of intraperitoneal hyperthermic perfusion chemotherapy combined with apatinib and tigio chemo⁃therapy in patients with simple exfoliative cytological positive gastric cancer

目的探讨腹腔热灌注紫杉醇化疗(hyperthermic intraperitoneal perfusion chemotherapy,HIPEC)联合阿帕替尼、替吉奥化疗对单纯脱落细胞学阳性胃癌(P0CY1)患者转化治疗的临床疗效及安全性。方法前瞻性纳入经腹腔镜探查后证实为P0CY1胃癌患者,所有患者均进行HIPEC联合阿帕替尼、替吉奥治疗,具体用药为:腹腔镜探查术后先给予患者3周期HIPEC化疗(紫杉醇75 mg/m2),HIPEC治疗结束14 d后开始进行连续21 d口服阿帕替尼500 mg/d;同时连续14 d口服替吉奥80 mg/(m2·d),停药7 d,每3周为1疗程。在进行3周期转化治疗后再次进行腹腔镜探查术,主要研究终点是腹腔内游离癌细胞转阴率及R0切除率,次要研究终点为总生存时间(OS)、无进展生存时间(PFS)、客观缓解率(ORR)、疾病控制率(DCR)以及安全性指标。结果自2018年2月5日至12月31日有277例进展期胃癌患者经腹腔镜探查后共入组38例(13.72%)P0CY1患者,全组中位年龄54岁。经3周期转化治疗后评估,ORR为52.63%(20/38),DCR为89.47%(34/38),所有患者均进行二次腹腔镜探查,腹腔内游离癌细胞转阴率为42.11%,转阴患者均行R0手术切除。中位随访时间16.4个月,中位生存期(mOS)为14.9个月,1年OS为65.79%;中位无进展生存期(mPFS)为11.7个月,1年PFS为50.00%。主要化疗不良反应是Ⅰ-Ⅱ级血液毒性反应及消化道反应,所有病例均未发生转化治疗和手术治疗相关的死亡。结论HIPEC紫杉醇化疗联合阿帕替尼、替吉奥治疗可以作为P0CY1胃癌患者转化治疗的一种选择,能够显著延长无进展生存期,且化疗不良反应可控,是一种安全有效的转化治疗方案。

Objective To explore the clinical efficacy and safety of hyperthermic intraperitoneal perfusion chemotherapy(HIPEC)combined with apatinib and tigio chemotherapy for conversion therapy of patients with sim⁃ple exfoliative cytology⁃positive gastric cancer(P0CY1).Methods Prospective study included patients with P0CY1 gastric cancer confirmed by laparoscopic exploration.All patients were treated with HIPEC combined with apatinib and tigio.The specific drugs were as follows:three cycles of HIPEC chemotherapy were given to the patients after laparoscopic exploration(paclitaxel 75 mg/m2),HIPEC began to take apatinib 500 mg daily for 21 days after 14 days of paclitaxel 75 mg/m2),HIPEC treatment,and oral tigio 80 mg/m2.for 14 days after laparoscopic exploration.D),was stopped for 7 days,and every 3 weeks was a course of treatment.Laparoscopic exploration was performed again after 3 cycles of conversion therapy.the main end points were the negative conversion rate of intraperitoneal free cancer cells and the resection rate of R0,while the secondary end points were total survival time(OS),progression⁃free survival time(PFS),objective remission rate(ORR),disease control rate(DCR)and safety indicators.Results From 2018⁃02⁃05 to 2018⁃12⁃31,277 patients with advanced gastric cancer were enrolled in a total of 38 patients(13.72%)with P0CY1 after laparoscopic exploration,with a median age of 54 years.After 3 cycles of conversion therapy,the ORR was 52.63%(20/38),DCR was 89.47%(34/38).All patients underwent secondary laparoscopic exploration,and the negative conversion rate of free cancer cells in the abdominal cavity was 42.11%.All patients were resected by R0 operation.The median follow⁃up time was 16.4 months,the median survival time(mOS)was 14.9 months,the 1⁃year OS was 65.79%,the median progression⁃free survival time(mPFS)was 11.7 months,and the 1⁃year PFS was 50.00%.The main adverse reactions of chemotherapy wereⅠ~Ⅱgrade hematotoxicity and digestive tract reactions,and there was no death related to conversion therapy and surgical treatment in all cases.Conclusion HIPEC chemotherapy combined with apatinib and tigio can be used as a choice of conversion therapy for patients with P0CY1 gastric cancer,which can significantly prolong the progression⁃free survival time,and the adverse reactions of chemotherapy can be controlled.It is a safe and effec⁃tive conversion therapy,which is worthy of further study.