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

F. E. Buisman, M. Y. V. Homs, D. J. Grünhagen, W. F. Filipe, R. J. Bennink, M. G. H. Besselink, I. H. M. Borel Rinkes, R. C. G. Bruijnen, A. Cercek, M. I. D’Angelica, O. M. van Delden, M. L. Donswijk, L. van Doorn, P. G. Doornebosch, J. Emmering, J. I. Erdmann, N. S. IJzerman, C. Grootscholten, J. Hagendoorn, N. E. Kemeny & 22 others T. P. Kingham, E. G. Klompenhouwer, N. F. M. Kok, S. Koolen, K. F. D. Kuhlmann, M. C. Kuiper, M. G. E. Lam, R. H. J. Mathijssen, A. Moelker, E. Oomen-de Hoop, C. J. A. Punt, W. W. te Riele, J. M. L. Roodhart, R. J. Swijnenburg, W. Prevoo, P. J. Tanis, M. Vermaas, M. W. J. Versleijen, F. P. Veuger, M. J. Weterman, C. Verhoef, B. Groot Koerkamp

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Article number327
JournalBMC Cancer
Volume19
Issue number1
DOIs
Publication statusPublished - 2019

Cite this

Buisman, F. E. ; Homs, M. Y. V. ; Grünhagen, D. J. ; Filipe, W. F. ; Bennink, R. J. ; Besselink, M. G. H. ; Borel Rinkes, I. H. M. ; Bruijnen, R. C. G. ; Cercek, A. ; D’Angelica, M. I. ; van Delden, O. M. ; Donswijk, M. L. ; van Doorn, L. ; Doornebosch, P. G. ; Emmering, J. ; Erdmann, J. I. ; IJzerman, N. S. ; Grootscholten, C. ; Hagendoorn, J. ; Kemeny, N. E. ; Kingham, T. P. ; Klompenhouwer, E. G. ; Kok, N. F. M. ; Koolen, S. ; Kuhlmann, K. F. D. ; Kuiper, M. C. ; Lam, M. G. E. ; Mathijssen, R. H. J. ; Moelker, A. ; Oomen-de Hoop, E. ; Punt, C. J. A. ; te Riele, W. W. ; Roodhart, J. M. L. ; Swijnenburg, R. J. ; Prevoo, W. ; Tanis, P. J. ; Vermaas, M. ; Versleijen, M. W. J. ; Veuger, F. P. ; Weterman, M. J. ; Verhoef, C. ; Groot Koerkamp, B. / 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. In: BMC Cancer. 2019 ; Vol. 19, No. 1.
@article{cbc2c293dd1048d4a6f545950c9ab12a,
title = "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",
abstract = "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.",
author = "Buisman, {F. E.} and Homs, {M. Y. V.} and Gr{\"u}nhagen, {D. J.} and Filipe, {W. F.} and Bennink, {R. J.} and Besselink, {M. G. H.} and {Borel Rinkes}, {I. H. M.} and Bruijnen, {R. C. G.} and A. Cercek and D’Angelica, {M. I.} and {van Delden}, {O. M.} and Donswijk, {M. L.} and {van Doorn}, L. and Doornebosch, {P. G.} and J. Emmering and Erdmann, {J. I.} and IJzerman, {N. S.} and C. Grootscholten and J. Hagendoorn and Kemeny, {N. E.} and Kingham, {T. P.} and Klompenhouwer, {E. G.} and Kok, {N. F. M.} and S. Koolen and Kuhlmann, {K. F. D.} and Kuiper, {M. C.} and Lam, {M. G. E.} and Mathijssen, {R. H. J.} and A. Moelker and {Oomen-de Hoop}, E. and Punt, {C. J. A.} and {te Riele}, {W. W.} and Roodhart, {J. M. L.} and Swijnenburg, {R. J.} and W. Prevoo and Tanis, {P. J.} and M. Vermaas and Versleijen, {M. W. J.} and Veuger, {F. P.} and Weterman, {M. J.} and C. Verhoef and {Groot Koerkamp}, B.",
year = "2019",
doi = "10.1186/s12885-019-5515-6",
language = "English",
volume = "19",
journal = "BMC Cancer",
issn = "1471-2407",
publisher = "BioMed Central",
number = "1",

}

Buisman, FE, Homs, MYV, Grünhagen, DJ, Filipe, WF, Bennink, RJ, Besselink, MGH, Borel Rinkes, IHM, Bruijnen, RCG, Cercek, A, D’Angelica, MI, van Delden, OM, Donswijk, ML, van Doorn, L, Doornebosch, PG, Emmering, J, Erdmann, JI, IJzerman, NS, Grootscholten, C, Hagendoorn, J, Kemeny, NE, Kingham, TP, Klompenhouwer, EG, Kok, NFM, Koolen, S, Kuhlmann, KFD, Kuiper, MC, Lam, MGE, Mathijssen, RHJ, Moelker, A, Oomen-de Hoop, E, Punt, CJA, te Riele, WW, Roodhart, JML, Swijnenburg, RJ, Prevoo, W, Tanis, PJ, Vermaas, M, Versleijen, MWJ, Veuger, FP, Weterman, MJ, Verhoef, C & Groot Koerkamp, B 2019, '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' BMC Cancer, vol. 19, no. 1, 327. https://doi.org/10.1186/s12885-019-5515-6

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

In: BMC Cancer, Vol. 19, No. 1, 327, 2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - 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

AU - Buisman, F. E.

AU - Homs, M. Y. V.

AU - Grünhagen, D. J.

AU - Filipe, W. F.

AU - Bennink, R. J.

AU - Besselink, M. G. H.

AU - Borel Rinkes, I. H. M.

AU - Bruijnen, R. C. G.

AU - Cercek, A.

AU - D’Angelica, M. I.

AU - van Delden, O. M.

AU - Donswijk, M. L.

AU - van Doorn, L.

AU - Doornebosch, P. G.

AU - Emmering, J.

AU - Erdmann, J. I.

AU - IJzerman, N. S.

AU - Grootscholten, C.

AU - Hagendoorn, J.

AU - Kemeny, N. E.

AU - Kingham, T. P.

AU - Klompenhouwer, E. G.

AU - Kok, N. F. M.

AU - Koolen, S.

AU - Kuhlmann, K. F. D.

AU - Kuiper, M. C.

AU - Lam, M. G. E.

AU - Mathijssen, R. H. J.

AU - Moelker, A.

AU - Oomen-de Hoop, E.

AU - Punt, C. J. A.

AU - te Riele, W. W.

AU - Roodhart, J. M. L.

AU - Swijnenburg, R. J.

AU - Prevoo, W.

AU - Tanis, P. J.

AU - Vermaas, M.

AU - Versleijen, M. W. J.

AU - Veuger, F. P.

AU - Weterman, M. J.

AU - Verhoef, C.

AU - Groot Koerkamp, B.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85063963854&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/30953467

U2 - 10.1186/s12885-019-5515-6

DO - 10.1186/s12885-019-5515-6

M3 - Article

VL - 19

JO - BMC Cancer

JF - BMC Cancer

SN - 1471-2407

IS - 1

M1 - 327

ER -