Journal Article

Adjuvant hepatic arterial infusion pump chemotherapy and resection versus resection alone in patients with low-risk resectable colorectal liver metastases – the multicenter randomized controlled PUMP trial

Oomen-de Hoop, E., Cercek, A., Hagendoorn, J., Kingham, T. P., Tanis, P. J., Emmering, J., Verhoef, C., Besselink, M. G. H., Borel Rinkes, I. H. M., van Doorn, L., Doornebosch, P. G., Mathijssen, R. H. J., Bennink, R. J., Erdmann, J. I., Koolen, S., Filipe, W. F., Klompenhouwer, E. G., D’Angelica, M. I., Weterman, M. J., Veuger, F. P., IJzerman, N. S., Moelker, A., Versleijen, M. W. J., Swijnenburg, R. J., Prevoo, W., Donswijk, M. L., Roodhart, J. M. L., Grünhagen, D. J., Kok, N. F. M., Homs, M. Y. V., Bruijnen, R. C. G., te Riele, W. W., Buisman, F. E., Vermaas, M., Kemeny, N. E., van Delden, O. M., Kuhlmann, K. F. D., Punt, C. J. A., Lam, M. G. E., Grootscholten, C., Kuiper, M. C., Groot Koerkamp, B.

2019

Overview

Background 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. Methods 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. Discussion 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. Trial registration The PUMP trial is registered in the Netherlands Trial Register (NTR), number: 7493 . Date of registration September 23, 2018.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adjuvant chemotherapy / Adult / Analysis / Angiography / Antigens / Antimetabolites, Antineoplastic - administration & dosage / Biological markers / Biomedical and Life Sciences / Biomedicine / cancer imaging / Cancer metastasis / Cancer patients / Cancer Research / Cancer therapies / Carcinoembryonic antigen / Care and treatment / CAT scans / Chemotherapy / Chemotherapy, Adjuvant - instrumentation / Chemotherapy, Adjuvant - methods / Clinical trials / Clinical Trials, Phase III as Topic / Colorectal cancer / Colorectal carcinoma / Colorectal liver metastasis / Colorectal Neoplasms - mortality / Colorectal Neoplasms - pathology / Diagnostic imaging / Floxuridine - administration & dosage / Health aspects / Health Promotion and Disease Prevention / Hepatectomy / Hepatic arterial infusion / Humans / Infusion Pumps, Implantable / Infusions, Intra-Arterial - instrumentation / Infusions, Intra-Arterial - methods / interventional therapeutics / Labels / Liver / Liver cancer / Liver Neoplasms - mortality / Liver Neoplasms - secondary / Liver Neoplasms - therapy / Medical imaging / Medical prognosis / Medicine/Public Health / Metastases / Metastasis / Multicenter Studies as Topic / Neoplasm Recurrence, Local - prevention & control / Netherlands / Oncology / Patients / Perfusion / Pharmacokinetics / Progression-Free Survival / Prostheses and implants / Quality of life / Randomized Controlled Trials as Topic / Resection / Retrospective Studies / Scintigraphy / Studies / Study Protocol / Surgery / Surgical Oncology / Survival / Tumors / Veins & arteries / Young Adult