Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for borderline resectable and unresectable colorectal liver metastases: phase II feasibility study

Myrtle F Krul; Niels F M Kok; Harun Osmani; Florian E Buisman; Bas Groot Koerkamp; Dirk J Grunhagen; Cornelis Verhoef; Bianca Mostert; Petur Snaebjornsson; Bram Westerink; Elisabeth G Klompenhouwer; Maarten L Donswijk; Theo J M Ruers; Joeri A J Douma; Nico van Blijderveen; T Peter Kingham; Michael I D'Angelica; Nancy E Kemeny; Karen Bolhuis; Tineke E Buffart; Koert F D Kuhlmann

doi:10.1093/bjs/znae089

Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for borderline resectable and unresectable colorectal liver metastases: phase II feasibility study

Myrtle F Krul^*, Niels F M Kok, Harun Osmani, Florian E Buisman, Bas Groot Koerkamp, Dirk J Grunhagen, Cornelis Verhoef, Bianca Mostert, Petur Snaebjornsson, Bram Westerink, Elisabeth G Klompenhouwer, Maarten L Donswijk, Theo J M Ruers, Joeri A J Douma, Nico van Blijderveen, T Peter Kingham, Michael I D'Angelica, Nancy E Kemeny, Karen Bolhuis, Tineke E BuffartKoert F D Kuhlmann

^*Corresponding author for this work

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Abstract

BACKGROUND:

Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy (HAIP-SYS) for liver-only colorectal liver metastases (CRLMs) has shown promising results but has not been adopted worldwide. This study evaluated the feasibility of HAIP-SYS in the Netherlands.

METHODS:

This was a single-arm phase II study of patients with CRLMs who received HAIP-SYS consisting of floxuridine with concomitant systemic FOLFOX or FOLFIRI. Main inclusion and exclusion criteria were borderline resectable or unresectable liver-only metastases, suitable arterial anatomy and no previous local treatment. Patients underwent laparotomy for pump implantation and primary tumour resection if in situ. Primary end point was feasibility, defined as ≥70% of patients completing two cycles of HAIP-SYS. Sample size calculations led to 31 patients. Secondary outcomes included safety and tumour response.

RESULTS:

Thirty-one patients with median 13 CRLMs (i.q.r. 6-23) were included. Twenty-eight patients (90%) received two HAIP-SYS cycles. Three patients did not get two cycles due to extrahepatic disease at pump placement, definitive pathology of a recto-sigmoidal squamous cell carcinoma, and progressive disease. Five patients experienced grade 3 surgical or pump device-related complications (16%) and 11 patients experienced grade ≥3 chemotherapy toxicity (38%). At first radiological evaluation, disease control rate was 83% (24/29 patients) and hepatic disease control rate 93% (27/29 patients). At 6 months, 19 patients (66%) had experienced grade ≥3 chemotherapy toxicity and the disease control rate was 79%.

CONCLUSION:

HAIP-SYS for borderline resectable and unresectable CRLMs was feasible and safe in the Netherlands. This has led to a successive multicentre phase III randomized trial investigating oncological benefit (EUDRA-CT 2023-506194-35-00). Current trial registration number: clinicaltrials.gov (NCT04552093).

Original language	English
Journal	The British journal of surgery
Volume	111
Issue number	4
DOIs	https://doi.org/10.1093/bjs/znae089
Publication status	Published - Apr 2024

Bibliographical note

© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].

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10.1093/bjs/znae089

znae089Final published version, 357 KBLicence: Article 25fa Dutch Copyright Act

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Krul, M. F., Kok, N. F. M., Osmani, H., Buisman, F. E., Groot Koerkamp, B., Grunhagen, D. J., Verhoef, C., Mostert, B., Snaebjornsson, P., Westerink, B., Klompenhouwer, E. G., Donswijk, M. L., Ruers, T. J. M., Douma, J. A. J., van Blijderveen, N., Kingham, T. P., D'Angelica, M. I., Kemeny, N. E., Bolhuis, K., ... Kuhlmann, K. F. D. (2024). Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for borderline resectable and unresectable colorectal liver metastases: phase II feasibility study. The British journal of surgery, 111(4). https://doi.org/10.1093/bjs/znae089

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title = "Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for borderline resectable and unresectable colorectal liver metastases: phase II feasibility study",

abstract = "BACKGROUND: Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy (HAIP-SYS) for liver-only colorectal liver metastases (CRLMs) has shown promising results but has not been adopted worldwide. This study evaluated the feasibility of HAIP-SYS in the Netherlands.METHODS: This was a single-arm phase II study of patients with CRLMs who received HAIP-SYS consisting of floxuridine with concomitant systemic FOLFOX or FOLFIRI. Main inclusion and exclusion criteria were borderline resectable or unresectable liver-only metastases, suitable arterial anatomy and no previous local treatment. Patients underwent laparotomy for pump implantation and primary tumour resection if in situ. Primary end point was feasibility, defined as ≥70% of patients completing two cycles of HAIP-SYS. Sample size calculations led to 31 patients. Secondary outcomes included safety and tumour response.RESULTS: Thirty-one patients with median 13 CRLMs (i.q.r. 6-23) were included. Twenty-eight patients (90%) received two HAIP-SYS cycles. Three patients did not get two cycles due to extrahepatic disease at pump placement, definitive pathology of a recto-sigmoidal squamous cell carcinoma, and progressive disease. Five patients experienced grade 3 surgical or pump device-related complications (16%) and 11 patients experienced grade ≥3 chemotherapy toxicity (38%). At first radiological evaluation, disease control rate was 83% (24/29 patients) and hepatic disease control rate 93% (27/29 patients). At 6 months, 19 patients (66%) had experienced grade ≥3 chemotherapy toxicity and the disease control rate was 79%.CONCLUSION: HAIP-SYS for borderline resectable and unresectable CRLMs was feasible and safe in the Netherlands. This has led to a successive multicentre phase III randomized trial investigating oncological benefit (EUDRA-CT 2023-506194-35-00). Current trial registration number: clinicaltrials.gov (NCT04552093).",

author = "Krul, {Myrtle F} and Kok, {Niels F M} and Harun Osmani and Buisman, {Florian E} and {Groot Koerkamp}, Bas and Grunhagen, {Dirk J} and Cornelis Verhoef and Bianca Mostert and Petur Snaebjornsson and Bram Westerink and Klompenhouwer, {Elisabeth G} and Donswijk, {Maarten L} and Ruers, {Theo J M} and Douma, {Joeri A J} and {van Blijderveen}, Nico and Kingham, {T Peter} and D'Angelica, {Michael I} and Kemeny, {Nancy E} and Karen Bolhuis and Buffart, {Tineke E} and Kuhlmann, {Koert F D}",

note = "{\textcopyright} The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].",

year = "2024",

month = apr,

doi = "10.1093/bjs/znae089",

language = "English",

volume = "111",

journal = "The British journal of surgery",

issn = "0007-1323",

publisher = "Oxford University Press",

number = "4",

}

Krul, MF, Kok, NFM, Osmani, H, Buisman, FE , Groot Koerkamp, B , Grunhagen, DJ , Verhoef, C , Mostert, B, Snaebjornsson, P, Westerink, B, Klompenhouwer, EG, Donswijk, ML, Ruers, TJM, Douma, JAJ, van Blijderveen, N, Kingham, TP, D'Angelica, MI, Kemeny, NE, Bolhuis, K, Buffart, TE & Kuhlmann, KFD 2024, 'Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for borderline resectable and unresectable colorectal liver metastases: phase II feasibility study', The British journal of surgery, vol. 111, no. 4. https://doi.org/10.1093/bjs/znae089

Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for borderline resectable and unresectable colorectal liver metastases: phase II feasibility study. / Krul, Myrtle F; Kok, Niels F M; Osmani, Harun et al.
In: The British journal of surgery, Vol. 111, No. 4, 04.2024.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for borderline resectable and unresectable colorectal liver metastases

T2 - phase II feasibility study

AU - Krul, Myrtle F

AU - Kok, Niels F M

AU - Osmani, Harun

AU - Buisman, Florian E

AU - Groot Koerkamp, Bas

AU - Grunhagen, Dirk J

AU - Verhoef, Cornelis

AU - Mostert, Bianca

AU - Snaebjornsson, Petur

AU - Westerink, Bram

AU - Klompenhouwer, Elisabeth G

AU - Donswijk, Maarten L

AU - Ruers, Theo J M

AU - Douma, Joeri A J

AU - van Blijderveen, Nico

AU - Kingham, T Peter

AU - D'Angelica, Michael I

AU - Kemeny, Nancy E

AU - Bolhuis, Karen

AU - Buffart, Tineke E

AU - Kuhlmann, Koert F D

N1 - © The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].

PY - 2024/4

Y1 - 2024/4

N2 - BACKGROUND: Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy (HAIP-SYS) for liver-only colorectal liver metastases (CRLMs) has shown promising results but has not been adopted worldwide. This study evaluated the feasibility of HAIP-SYS in the Netherlands.METHODS: This was a single-arm phase II study of patients with CRLMs who received HAIP-SYS consisting of floxuridine with concomitant systemic FOLFOX or FOLFIRI. Main inclusion and exclusion criteria were borderline resectable or unresectable liver-only metastases, suitable arterial anatomy and no previous local treatment. Patients underwent laparotomy for pump implantation and primary tumour resection if in situ. Primary end point was feasibility, defined as ≥70% of patients completing two cycles of HAIP-SYS. Sample size calculations led to 31 patients. Secondary outcomes included safety and tumour response.RESULTS: Thirty-one patients with median 13 CRLMs (i.q.r. 6-23) were included. Twenty-eight patients (90%) received two HAIP-SYS cycles. Three patients did not get two cycles due to extrahepatic disease at pump placement, definitive pathology of a recto-sigmoidal squamous cell carcinoma, and progressive disease. Five patients experienced grade 3 surgical or pump device-related complications (16%) and 11 patients experienced grade ≥3 chemotherapy toxicity (38%). At first radiological evaluation, disease control rate was 83% (24/29 patients) and hepatic disease control rate 93% (27/29 patients). At 6 months, 19 patients (66%) had experienced grade ≥3 chemotherapy toxicity and the disease control rate was 79%.CONCLUSION: HAIP-SYS for borderline resectable and unresectable CRLMs was feasible and safe in the Netherlands. This has led to a successive multicentre phase III randomized trial investigating oncological benefit (EUDRA-CT 2023-506194-35-00). Current trial registration number: clinicaltrials.gov (NCT04552093).

AB - BACKGROUND: Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy (HAIP-SYS) for liver-only colorectal liver metastases (CRLMs) has shown promising results but has not been adopted worldwide. This study evaluated the feasibility of HAIP-SYS in the Netherlands.METHODS: This was a single-arm phase II study of patients with CRLMs who received HAIP-SYS consisting of floxuridine with concomitant systemic FOLFOX or FOLFIRI. Main inclusion and exclusion criteria were borderline resectable or unresectable liver-only metastases, suitable arterial anatomy and no previous local treatment. Patients underwent laparotomy for pump implantation and primary tumour resection if in situ. Primary end point was feasibility, defined as ≥70% of patients completing two cycles of HAIP-SYS. Sample size calculations led to 31 patients. Secondary outcomes included safety and tumour response.RESULTS: Thirty-one patients with median 13 CRLMs (i.q.r. 6-23) were included. Twenty-eight patients (90%) received two HAIP-SYS cycles. Three patients did not get two cycles due to extrahepatic disease at pump placement, definitive pathology of a recto-sigmoidal squamous cell carcinoma, and progressive disease. Five patients experienced grade 3 surgical or pump device-related complications (16%) and 11 patients experienced grade ≥3 chemotherapy toxicity (38%). At first radiological evaluation, disease control rate was 83% (24/29 patients) and hepatic disease control rate 93% (27/29 patients). At 6 months, 19 patients (66%) had experienced grade ≥3 chemotherapy toxicity and the disease control rate was 79%.CONCLUSION: HAIP-SYS for borderline resectable and unresectable CRLMs was feasible and safe in the Netherlands. This has led to a successive multicentre phase III randomized trial investigating oncological benefit (EUDRA-CT 2023-506194-35-00). Current trial registration number: clinicaltrials.gov (NCT04552093).

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U2 - 10.1093/bjs/znae089

DO - 10.1093/bjs/znae089

M3 - Article

C2 - 38608150

SN - 0007-1323

VL - 111

JO - The British journal of surgery

JF - The British journal of surgery

IS - 4

ER -

Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for borderline resectable and unresectable colorectal liver metastases: phase II feasibility study

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