Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands.
Department of Surgery, Sint Antonius Hospital, Nieuwegein, The Netherlands.
BMJ Open. 2019 Jul 27;9(7):e030408. doi: 10.1136/bmjopen-2019-030408.
Repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX) is offered as a palliative treatment option for patients with isolated unresectable colorectal peritoneal metastases (PM) in several centres worldwide. However, little is known about its feasibility, safety, tolerability, efficacy, costs and pharmacokinetics in this setting. This study aims to explore these parameters in patients with isolated unresectable colorectal PM who receive repetitive ePIPAC-OX as a palliative monotherapy.
This multicentre, open-label, single-arm, phase II study is performed in two Dutch tertiary referral hospitals for the surgical treatment of colorectal PM. Eligible patients are adults who have histologically or cytologically proven isolated unresectable PM of a colorectal or appendiceal carcinoma, a good performance status, adequate organ functions and no symptoms of gastrointestinal obstruction. Instead of standard palliative treatment, enrolled patients receive laparoscopy-controlled ePIPAC-OX (92 mg/m body surface area (BSA)) with intravenous leucovorin (20 mg/m BSA) and bolus 5-fluorouracil (400 mg/m BSA) every 6 weeks. Four weeks after each procedure, patients undergo clinical, radiological and biochemical evaluation. ePIPAC-OX is repeated until disease progression, after which standard palliative treatment is (re)considered. The primary outcome is the number of patients with major toxicity (grade ≥3 according to the Common Terminology Criteria for Adverse Events v4.0) up to 4 weeks after the last ePIPAC-OX. Secondary outcomes are the environmental safety of ePIPAC-OX, procedure-related characteristics, minor toxicity, postoperative complications, hospital stay, readmissions, quality of life, costs, pharmacokinetics of oxaliplatin, progression-free survival, overall survival, and the radiological, histopathological, cytological, biochemical and macroscopic tumour response.
This study is approved by an ethics committee, the Dutch competent authority and the institutional review boards of both study centres. Results are intended for publication in peer-reviewed medical journals and for presentation to patients, healthcare professionals and other stakeholders.
NCT03246321, Pre-results; ISRCTN89947480, Pre-results; NTR6603, Pre-results; EudraCT: 2017-000927-29, Pre-results.
重复静电加压腹腔内气溶胶化疗联合奥沙利铂（ePIPAC-OX）已在全球多个中心被作为一种姑息治疗选择，用于治疗孤立性不可切除的结直肠腹膜转移（PM）患者。然而，对于接受这种姑息性单药治疗的孤立性不可切除结直肠 PM 患者，我们对于其可行性、安全性、耐受性、疗效、成本和药代动力学等参数知之甚少。本研究旨在探索接受重复 ePIPAC-OX 治疗的此类患者的这些参数。
这是一项在荷兰两家三级转诊医院进行的多中心、开放标签、单臂、二期研究，针对的是经组织学或细胞学证实的孤立性不可切除的结直肠或阑尾腺癌的 PM 患者。合格的患者为成人，具有良好的体能状态、足够的器官功能，并且没有胃肠道梗阻的症状。入组患者接受腹腔镜控制的 ePIPAC-OX（92mg/m2 体表面积（BSA））联合静脉注射亚叶酸（20mg/m2 BSA）和氟尿嘧啶推注（400mg/m2 BSA），每 6 周一次，而不是标准的姑息治疗。在每次操作后 4 周，患者接受临床、影像学和生化评估。在疾病进展后，ePIPAC-OX 将重复进行，直至疾病进展，之后将考虑（重新）采用标准姑息治疗。主要结局是在最后一次 ePIPAC-OX 后 4 周内发生主要毒性（根据通用术语标准 4.0 版，≥3 级）的患者数量。次要结局包括 ePIPAC-OX 的环境安全性、与操作相关的特征、轻微毒性、术后并发症、住院时间、再入院、生活质量、成本、奥沙利铂的药代动力学、无进展生存期、总生存期以及影像学、组织病理学、细胞学、生化和宏观肿瘤反应。
本研究已获得伦理委员会、荷兰主管部门和两个研究中心机构审查委员会的批准。研究结果旨在发表在同行评议的医学期刊上，并向患者、医疗保健专业人员和其他利益相关者展示。
NCT03246321，预注册；ISRCTN89947480，预注册；NTR6603，预注册；EudraCT：2017-000927-29，预注册。
