Reduced Floxuridine Dose Limits Hepatobiliary Toxicity Without Negatively Impacting Survival After Resection of...

Hepatic arterial infusion (HAI) of floxuridine is an effective adjuvant therapy for colorectal liver metastases (CRLM) following complete resection, but its use is limited by hepatobiliary toxicity. Dosing characteristics, factors associated with dose reductions, and the impact of starting dose on hepatobiliary toxicity and survival in the adjuvant setting are poorly described.

From 2015 to 2024, patients who received adjuvant HAI floxuridine after complete CRLM resection at City of Hope were included. Hepatobiliary toxicity and oncologic outcomes of standard (0.12 mg/kg/day) versus reduced (0.08 mg/kg/day) dosing were compared. Extent of hepatobiliary toxicity, factors associated with dose reductions, hepatic recurrence-free survival (H-RFS), and overall survival (OS) were examined.

Seventy-one patients were included (median age 52). Dosing information was available for 69 patients with 40 (58%) receiving the standard dose and 29 (42%) receiving the reduced dose. Patients receiving the standard dose had significantly higher rates of hepatobiliary toxicity, including increased transaminases, alkaline phosphatase, and bilirubin levels. Biliary sclerosis requiring endoscopic intervention occurred only in the standard-dose group (n = 4, 10%). Dose reductions were more frequent in the standard-dose group (82% vs. 53%, p = 0.04). Despite lower cumulative floxuridine exposure, the reduced dose did not compromise oncologic outcomes.

A reduced starting floxuridine dose (0.08 mg/kg/day) is associated with lower hepatobiliary toxicity without compromising survival after complete resection of CRLM. These findings support adopting the reduced dose as a new standard in the adjuvant treatment of resected CRLM.