Labadie Kevin P, Fan Darrell, Dominguez Dana A, Wong Paul, Meshkin Elizabeth, Vien Peter, Lau S Cecilia, Kessler Jonathan, Wagman Lawrence D, Fong Yuman, Fakih Marwan G, Melstrom Laleh G
Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA.
Department of Pharmacy Services, City of Hope National Medical Center, Duarte, CA, USA.
Ann Surg Oncol. 2025 Jul 22. doi: 10.1245/s10434-025-17783-y.
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.
氟尿苷肝动脉灌注（HAI）是结直肠癌肝转移（CRLM）完全切除术后一种有效的辅助治疗方法，但其使用受到肝胆毒性的限制。在辅助治疗中，给药特征、与剂量减少相关的因素以及起始剂量对肝胆毒性和生存的影响描述甚少。
纳入2015年至2024年在希望之城接受CRLM完全切除术后辅助HAI氟尿苷治疗的患者。比较标准剂量（0.12 mg/kg/天）与减量剂量（0.08 mg/kg/天）的肝胆毒性和肿瘤学结局。研究了肝胆毒性程度、与剂量减少相关的因素、无肝复发生存期（H-RFS）和总生存期（OS）。
纳入71例患者（中位年龄52岁）。69例患者有给药信息，其中40例（58%）接受标准剂量，29例（42%）接受减量剂量。接受标准剂量的患者肝胆毒性发生率显著更高，包括转氨酶、碱性磷酸酶和胆红素水平升高。仅标准剂量组发生了需要内镜干预的胆汁硬化（n = 4，10%）。标准剂量组剂量减少更频繁（82%对53%，p = 0.04）。尽管氟尿苷累积暴露量较低，但减量剂量并未影响肿瘤学结局。
氟尿苷起始剂量降低（0.08 mg/kg/天）与较低的肝胆毒性相关，且不影响CRLM完全切除术后的生存率。这些发现支持采用减量剂量作为切除CRLM辅助治疗的新标准。
