Systemic exposure of floxuridine after hepatic arterial infusion pump chemotherapy with floxuridine in patients with resected colorectal liver metastases

Nikki S IJzerman, Wills F Filipe, Peter de Bruijn, Florian E Buisman, Leni van Doorn, Pascal G Doornebosch, Jessica J Holster, Cecile Grootscholten, Dirk J Grünhagen, Christian P E van Bommel, Marjolein Y V Homs, Niels F M Kok, Cornelis Verhoef, Bas Groot Koerkamp, Koert F D Kuhlmann, Ron H J Mathijssen, Stijn L W Koolen

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Abstract

BACKGROUND: Floxuridine's high hepatic extraction ratio and short elimination half-life allows maximum liver exposure with minimal systemic side-effects. This study attempts to quantify the systemic exposure of floxuridine.

METHODS: Patients undergoing continuous hepatic arterial infusion pump (HAIP) floxuridine after resection of colorectal liver metastases (CRLM) in two centres underwent six cycles of floxuridine at start dose 0.12 mg/kg/day. No concomitant systemic chemotherapy was administered. Peripheral venous blood samples were drawn during the first two cycles: pre-dose (only in the second cycle), 30 min, 1 h, 2 h, 7 h, and 15 days after floxuridine infusion. Foxuridine concentration in the residual pump reservoir was measured on day 15 of both cycles. A floxuridine assay with a lower boundary of detection of 0.250 ng/mL was developed.

RESULTS: 265 blood samples were collected in the 25 patient included in this study. Floxuridine was mostly measurable at day 7 and day 15 (86 % and 88 % of patients respectively). The median dose corrected concentrations were 0.607 ng/mL [IQR: 0.472-0.747] for cycle 1 day 7, 0.579 ng/mL [IQR: 0.470-0.693] for cycle 1 day 15, 0.646 ng/mL [IQR: 0.463-0.8546] for cycle 2 day 7, and 0.534 ng/mL [IQR: 0.4257-0.7075] for cycle 2 day 15. One patient had remarkably high floxuridine concentrations reaching up to 44 ng/mL during the second cycle, without a clear explanation. The floxuridine concentration in the pump decreased by 14.7 % (range 0.5 %-37.8 %) over a period of 15 days (n = 18).

CONCLUSION: Overall, negligible systemic concentrations of floxuridine were detected. However, remarkably increased levels were detected in one patient. Floxuridine concentration in the pump decreases over time.

Original languageEnglish
Article number114625
JournalBiomedicine and Pharmacotherapy
Volume162
Early online date12 Apr 2023
DOIs
Publication statusPublished - Jun 2023

Bibliographical note

Funding Information:
The current work is a side study of the PUMP trial (EUCTR2016–004299–24-NL), which is supported by the Dutch Cancer Society ( DCS; in Dutch: 'KWF Kankerbestrijding , the Netherlands (grant number 12077 , 2018 ).

Publisher Copyright:
© 2023

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