“植入用缓释顺铂”内镜下植入治疗晚期食管癌的Ⅱ_a期临床研究

Endoscopic treatment with sustained-release cisplatin for implant of advanced esophageal cancer:A phase Ⅱ_a clinical trail

目的:观察植入用缓释顺铂治疗晚期食管癌的安全性和有效性,并探索其合适给药剂量。方法:本研究为前瞻性、多中心、单臂Ⅱa期临床研究,计划入组病例24~32例。西京医院消化内科为本试验的分中心之一,共15例患者,其中60mg组2例,80mg组4例,100mg组9例。受试者于植药前、植药后1周、4周进行血生化、肝肾功能检查,观察与药物相关的不良反应。入组前进行内镜、CT、食道钡餐检查,4周再进行内镜、CT和食道钡餐复查,参照WHO实体肿瘤疗效评估标准,对比检验判断近期疗效。结果:本中心入组的15例中13例完成全部实验流程,可进行耐受性和不良反应评价。该试验未出现Ⅲ-Ⅳ度不良反应,已发生的实验室及症状性不良事件≤Ⅱ度,100mg组受试者有62.5%发生胸骨后疼痛。可进行肿瘤体积评估的10例病例CT显示疾病控制率(DCR)为90%(9例/10例)。根据疗效、不良反应及并发症分析结果,结合给药方法及剂量,拟定Ⅲ期临床研究以每厘米为一个层面,每一层面植药20mg作为临床试验用药单位剂量强度。结论:内镜引导下在食管肿瘤边缘区域和瘤内植入"植入用缓释顺铂粒子",对治疗晚期食管癌有一定的疗效,且临床耐受性较好,对于不能手术或者放弃手术的有吞咽困难的食管癌患者,可改善其食管梗阻症状。

Objective： To observe the safety and efficacy of sustained- release cisplatin for implant in the treatment of advanced esophageal cancer,and explore the suitable dose of its clinical application. Methods： The present study was a prospective,multicenter and single- arm phaseⅡa clinical trial,and 24 to 32 patients were planned to be enrolled. Department of gastroenterology in Xijing hospital was one of the sub- centers,15 patients were included. In the 15 patients,2 cases were administrated with 60 mg dose,4 with 80 mg,and 9 with 100 mg. Blood biochemistry,liver and kidney function were examined respectively before implant,1 week and 4 weeks after implant,and drug related adverse reactions were observed. Endoscopy,CT and esophageal barium meal examination were conducted before enrolled. Review above items at the fourth week,and judge the recent curative effect by reference to WHO solid tumor curative effect evaluation standard. Results： 13 cases of 15 patients completed all the trial processes and their tolerance and adverse reactions could be evaluated. There were no adverse reactions with Ⅲ to Ⅳ degree. The occurred symptomatic adverse events were less than Ⅱ degree. 62. 5% patients of 100 mg dose group had gotten chest pain. The results of 10 cases with evaluable tumor volume showed that DCR（ disease control rate） was 90%（ 9 /10）. Based on the efficacy,adverse reactions and complications results,we would suggest a drug clinical trials unit as 20 mg dose implantation per 1cm for a lever in future phase Ⅲ clinical trial. Conclusion： Implanting sustained- release cisplatin particles guided by endoscopy on the edge and in the esophageal tumor of advanced esophageal cancer,brought distinct curative effect and showed better clinical tolerance. For esophageal cancer patients with dysphagia,who were not suitable for operation,obstruction symptoms could be relieved through the present treatment.