Department of Surgery, Erasmus MC Cancer Institute, Erasmus University, Dr. Molewaterplein 40, 3015, GD, Rotterdam, The Netherlands.
Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, The Netherlands.
BMC Cancer. 2019 Apr 5;19(1):327. doi: 10.1186/s12885-019-5515-6.
Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) --the PUMP trial-- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM.
This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 μg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4-12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and a reduction of costs, compared to resection alone.
If this PUMP trial demonstrates that adjuvant HAIP chemotherapy improves survival in low-risk patients, this treatment approach may be implemented in the standard of care of patients with resected CRLM since adjuvant systemic chemotherapy alone has not improved survival.
The PUMP trial is registered in the Netherlands Trial Register (NTR), number: 7493 . Date of registration September 23, 2018.
结直肠肝转移（CRLM）切除术后，所有患者中有 70%报告复发，其中一半局限于肝脏。辅助肝动脉灌注泵（HAIP）化疗旨在降低肝内复发的风险。一项大型回顾性倾向评分分析表明，HAIP 化疗对具有低风险肿瘤特征的患者特别有效。这项随机对照试验（RCT）——PUMP 试验的目的是研究辅助 HAIP 化疗在可切除 CRLM 低风险患者中的疗效。
这是一项开放标签的多中心 RCT。共纳入 230 例无肝外疾病的可切除 CRLM 患者。只有临床风险评分（CRS）为 0 至 2 的患者符合条件，这意味着：患者最多允许有五个不良预后因素中的两个（无疾病间期<12 个月、结直肠癌阳性淋巴结、超过 1 个 CRLM、最大 CRLM 直径超过 5cm、血清癌胚抗原>200μg/L）。随机分配至 A 组的患者接受 CRLM 的完全切除术，不进行任何辅助治疗，这是荷兰的标准治疗方法。B 组患者在 CRLM 切除时植入可植入式泵，并在手术后 4-12 周开始辅助 HAIP 化疗，计划进行 6 个周期的氟尿嘧啶。主要终点是无进展生存期（PFS）。次要终点包括总生存期、肝 PFS、安全性、生活质量和成本效益。还将研究肝动脉内给予氟尿嘧啶的药代动力学以及 HAIP 化疗疗效的预测生物标志物。在一项辅助研究中，将比较 CT 血管造影与放射性核素闪烁扫描以检测肝外灌注，以评估 CT 血管造影的准确性。我们假设与单独切除相比，辅助 HAIP 化疗可提高生存率、改善生活质量并降低成本。
如果这项 PUMP 试验表明辅助 HAIP 化疗可改善低危患者的生存，那么这种治疗方法可能会被纳入可切除 CRLM 患者的标准治疗方法中，因为单独辅助全身化疗并未改善生存。
PUMP 试验在荷兰临床试验注册中心（NTR）注册，编号：7493。注册日期：2018 年 9 月 23 日。
