Chirurgia del Peritoneo e del Retroperitoneo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy.
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.
BMJ Open. 2022 Aug 1;12(8):e051324. doi: 10.1136/bmjopen-2021-051324.
Up to one-fifth of patients with colorectal cancer will develop peritoneal metastases, frequently without other districts' involvement. Despite the recent unsuccesses of hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer peritoneal metastases treatment, the rationale in the prophylactic setting remains strong. Several clinical and pharmacokinetic data suggest that the efficacy of intraperitoneal chemotherapy is highest when the disease is microscopic. However, robust evidence demonstrating whether the addition of HIPEC for high-risk colorectal cancers offers better control of local recurrence is lacking.
This is a multicentre randomised phase 3 trial comparing prophylactic surgery plus HIPEC CO2 with mitomycin, over standard surgical excision in patients with colorectal cancer at high risk of peritoneal carcinomatosis; 388 patients will be included in this study. The primary objective is to compare the efficacy of prophylactic surgery (radical colorectal resection, omentectomy, appendectomy, round ligament of the liver resection and bilateral adnexectomy) plus HIPEC CO2 with mitomycin and standard surgery in terms of local recurrence-free survival. The main secondary endpoints are disease-free survival (DFS), overall survival (OS) and safety. The primary endpoint will be described with a cumulative incidence function and will be analysed with Grey test to take account of the competing risks. DFS and OS will be described with the Kaplan-Meier method.
This trial has been evaluated by the Italian Medicines Agency, local ethics committees and will be submitted to the Ministry of Health to notify the start of the trial according to the regulation of trials on devices with CE mark/certification.The results will be submitted for presentation at academic meetings and for publication in a peer-reviewed journal, whatever the findings.
NCT03914820.
多达五分之一的结直肠癌患者会发生腹膜转移，且常无其他部位的累及。尽管近年来腹腔热灌注化疗（HIPEC）治疗结直肠癌腹膜转移的尝试并未成功，但预防性应用 HIPEC 的基本原理仍然合理。多项临床和药代动力学数据表明，当疾病处于微小时，腹腔内化疗的疗效最高。然而，目前尚缺乏有力证据证明对于高危结直肠癌患者，预防性应用 HIPEC 是否能更好地控制局部复发。
这是一项多中心随机 3 期临床试验，比较了高危结直肠癌患者预防性手术联合 CO2-HIPEC 与丝裂霉素治疗与标准手术切除的疗效；将纳入 388 例患者。主要目标是比较预防性手术（根治性结直肠切除术、大网膜切除术、阑尾切除术、圆韧带肝切除术和双侧附件切除术）联合 CO2-HIPEC 与丝裂霉素和标准手术治疗在局部无复发生存率方面的疗效。主要次要终点是无病生存（DFS）、总生存（OS）和安全性。主要终点将通过累积发生率函数进行描述，并采用 Grey 检验进行分析，以考虑竞争风险。DFS 和 OS 将采用 Kaplan-Meier 方法进行描述。
该试验已由意大利药品管理局、当地伦理委员会进行评估，并将提交给卫生部，根据带有 CE 标志/认证的器械试验规定，通知试验开始。无论结果如何，研究结果将提交学术会议展示，并发表在同行评议的期刊上。
NCT03914820。
