Concomitant intraperitoneal and systemic chemotherapy for extensive peritoneal metastases of colorectal origin: protocol of the multicentre, open-label, phase I, dose-escalation INTERACT trial
Concomitant intraperitoneal and systemic chemotherapy for extensive peritoneal metastases of colorectal origin: protocol of the multicentre, open-label, phase I, dose-escalation INTERACT trial
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DOI：
10.1136/bmjopen-2019-034508
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发表时间：
2019-12-01
期刊：
影响因子：
2.9
通讯作者：
Burger, Jacobus W. A.
中科院分区：
文献类型：
--
作者：
de Boer, Nadine Leonie;Brandt-Kerkhof, Alexandra R. M.;Burger, Jacobus W. A.
细胞减少手术和腹腔内高温化疗（CRS-HIPEC）已成为低/中度腹部疾病负荷的结直肠腹膜转移患者的标准治疗方法。在腹膜癌指数（PCI）评分为bbb20的情况下，CRS-HIPEC不被认为是有益的。PCI患者目前接受姑息性全身化疗。先前的研究表明，全身化疗对腹膜转移的效果不如对结直肠癌血液源性扩散的效果。提示腹膜转移患者在全身化疗的基础上增加腹腔化疗可能会受益。本研究的目的是建立伊立替康腹腔注射的最大耐受剂量，加入结肠直肠癌的标准护理系统治疗。次要终点是确定这种治疗的安全性和可行性，并建立腹腔注射伊立替康的药代动力学特征。方法和分析第一阶段“3+3”剂量递增研究在两个荷兰三级转诊中心进行。研究人群包括有广泛的结肠直肠腹膜转移的成年患者，他们的身体状况良好，没有腹外转移。根据CRS-HIPEC的标准检查，患者将接受诊断性腹腔镜检查以对PCI进行评分。在PCI bbb20的情况下，将在患者腹部放置一个腹膜通路口。通过这个港口，我们将给予伊立替康腹腔注射，联合标准的全身治疗，包括5-氟尿嘧啶/亚叶酸钙与奥沙利铂和靶向药物贝伐单抗。治疗包括最多12个周期，每2周。
Introduction Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has become standard of care for patients with peritoneal metastases of colorectal origin with a low/moderate abdominal disease load. In case of a peritoneal cancer index (PCI) score >20, CRS-HIPEC is not considered to be beneficial. Patients with a PCI >20 are currently offered palliative systemic chemotherapy. Previous studies have shown that systemic chemotherapy is less effective against peritoneal metastases than it is against haematogenous spread of colorectal cancer. It is suggested that patients with peritoneal metastases may benefit from the addition of intraperitoneal chemotherapy to systemic chemotherapy. Aim of this study is to establish the maximum tolerated dose of intraperitoneal irinotecan, added to standard of care systemic therapy for colorectal cancer. Secondary endpoints are to determine the safety and feasibility of this treatment and to establish the pharmacokinetic profile of intraperitoneally administered irinotecan.Methods and analysis This phase I, '3+3' dose-escalation, study is performed in two Dutch tertiary referral centres. The study population consists of adult patients with extensive peritoneal metastases of colorectal origin who have a good performance status and no extraabdominal metastases. According to standard work-up for CRS-HIPEC, patients will undergo a diagnostic laparoscopy to score the PCI. In case of a PCI >20, a peritoneal access port will be placed in the abdomen of the patient. Through this port we will administer intraperitoneal irinotecan, in combination with standard systemic treatment consisting of 5-fluorouracil/leucovorin with oxaliplatin and the targeted agent bevacizumab. Therapy consists of a maximum of 12 cycles 2-weekly.