Perioperative Outcomes and Technical Feasibility of A Phase II Trial of Hepatic Artery Infusional Floxuridine with Systemic Chemotherapy in Treatment of Pancreatic Cancer Liver Metastases

Authors

• Jason M. Aubrey, Corewell Health West Resident
• Mariam Khan, Corewell Health West Fellow
• Jesse Kelley, Corewell Health West Resident
• Hannah Liefeld, Corewell Health West Resident
• Kathrine Kelly
• Hordur M. Kolbeinsson, Corewell Health West
• M Mura Assifi, Corewell Health West
• Mathew Chung, Corewell Health West
• G Paul Wright, Corewell Health West

Document Type

Conference Proceeding

Publication Date

2-2025

Abstract

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) often metastasizes to the liver, leading to hepatic failure and limited survival. Hepatic artery infusion (HAI) chemotherapy with floxuridine (FUDR) has shown survival benefits in other liver malignancies but has not been applied to PDAC liver metastases. We hypothesize that combining HAI FUDR with systemic chemotherapy will improve survival in PDAC with liver metastases.

METHODS: Single-center, non-blinded, single-arm phase II clinical trial was conducted involving patients with synchronous PDAC liver metastases (NCT03856658). Patients underwent surgical placement of an HAI pump for FUDR delivery in 28-day cycles, combined with systemic chemotherapy selected by their oncologist. Management of the primary tumor included resection or irreversible electroporation during pump placement. The primary endpoint was 1-year hepatic progression-free survival, assessed using RECIST criteria (>20% growth in target lesions or new lesions). Secondary endpoint was overall survival.

RESULTS: A total of 13 patients were enrolled, with a mean age of 64 years (SD 9.5), 10 male (77%), and a mean BMI of 28 (SD 5.5). The primary tumor was resectable in 9 (69%) and locally advanced in 4 (31%). All patients received at least six cycles of neoadjuvant chemotherapy: 9 (69%) received FOLFIRINOX, and 4 (31%) Gemcitabine-Abraxane. Of the resectable tumors, 7 patients underwent distal pancreatectomy, 1 had pancreaticoduodenectomy, and 1 declined surgery. Irreversible electroporation was performed in 3 (75%) patients with locally advanced tumors. All patients received a Medtronic SynchroMed II pump. Average operative time was 268 minutes (SD 55) and length of stay was 5.8 days (SD 2.8). No in-hospital mortalities occurred. No patients showed extra-hepatic perfusion. The most common complication was chemical hepatitis and was seen in all patients, necessitating adjustments in FUDR dosing or scheduling. One patient required pump removal due to catheter dislodgement (8%). The median number of FUDR cycles received was five (range 1–6), with a mean dosage of 55% of the intended amount (range 20%–92%). At one year, 8 (62%) had hepatic progression free survival, 2 (15%) had progressive disease, 2 (15%) were deceased, and 1 (8%) enrolled in hospice. Currently, 10 of 13 patients are deceased, with a mean survival time of 466 days. The three surviving patients have been followed for a mean of 665 days with stable disease.

CONCLUSIONS: HAI FUDR combined with systemic chemotherapy shows potential to improve survival in PDAC patients with liver metastases. Further studies are needed to identify which patients may benefit from this therapy.

Comments

Advanced Cancer Therapies (ACT), February 14-17, 2025, Scottsdale, AZ

Recommended Citation

Aubrey JM, Khan M, Kelley J, Liefeld H, Kelly K, Kolbeinsson H, et al. [Assifi M, Chung M, Wright GP]. Perioperative outcomes and technical feasibility of a phase II trial of hepatic artery infusional floxuridine with systemic chemotherapy in treatment of pancreatic cancer liver metastases. American College of Surgeons Clinical Congress (ACS), 2025 Oct; Chicago, IL.