Systemic exposure of floxuridine after hepatic arterial infusion pump chemotherapy with floxuridine in patients with resected colorectal liver metastases - 29/04/23
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.
Il testo completo di questo articolo è disponibile in PDF.Graphical Abstract |
Highlights |
• | An assay was developed measuring serum floxuridine concentrations down to 0.25 ng/mL |
• | Negligible serum floxuridine concentrations were measured during the HAIP cycles |
• | Floxuridine concentration in the pump may gradually decline |
• | No floxuridine-attributed extrahepatic toxicity were detected |
Abbreviations : 5-FU, AST, CRLM, CTCAE, DPYD, GDA, HAIP, IQR, IU, LC-MS/MS, LLQ, MAA, MRM, PK, SD, UPLC
Keywords : Pharmacokinetics, Hepatic arterial infusion pump chemotherapy, Floxuridine, Colorectal liver metastases
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Vol 162
Articolo 114625- Giugno 2023 Ritorno al numeroBenvenuto su EM|consulte, il riferimento dei professionisti della salute.
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