Hepatic Arterial Infusion of Chemotherapy for Advanced Hepatobiliary Cancers: State of the Art

Abstract

Liver functional failure is one of the leading causes of cancer-related death. Primary liver tumors grow up mainly in the liver, and thus happens for liver metastases deriving from other organs having a lower burden of disease at the primary site. Systemic chemotherapy usually offers a modest benefit in terms of disease control rate, progression-free survival, and overall survival at the cost of a significant percentage of adverse events. Liver malignancies are mostly perfused by the hepatic artery while the normal liver parenchyma by the portal vein network. On these bases, the therapeutic strategy consisting of hepatic arterial infusion (HAI) of chemotherapy takes place. In literature, HAI chemotherapy was applied for the treatment of advanced hepatobiliary cancers with encouraging results. Different chemotherapeutic agents were used such as Oxaliplatin, Cisplatin, Gemcitabine, Floxuridine, 5-Fluorouracil, Epirubicin, individually or in combination. However, the efficacy of this treatment strategy remains controversial. Therefore, this review aims to summarize the current knowledge on this approach from different points of view, such as techniques, drugs pharmacology and pharmacokinetics, and clinical outcomes for advanced hepatobiliary cancers.

Analysis of Hepatic Artery Infusion (HAI) Chemotherapy Using Randomized Trials of Floxuridine (FUDR) for Colon Cancer Patients with Multiple Liver Metastases

“…The liver's collateral blood flow allows for the blockage of abnormal lobar arteries and the following crossover perfusion by vessels which are nonligated. In the case of abnormal HA architecture, this makes catheter placement easier [ 23 ].…”

Intra-Arterial Infusion Chemotherapy in Advanced Pancreatic Cancer: A Comprehensive Review

“…Moreover, the infusion of an initial bolus allows the therapeutic window to be reached more rapidly, which is then sustained by the subsequent c.i. Literature data have already evaluated the 5-FU liver extraction rate after HAI, which is approximately 75–80% [ 24 ], and several clinical trials have demonstrated remarkable efficacy in the treatment of primary and secondary hepatic malignancies. Tao et al tested the pharmacokinetic differences between PAI and the intravenous infusion of 5-FU in a Wistar rat model.…”

“…In summary, the poor prognosis, the limited treatment strategies, and the anatomical and biological features of PC justify the medical need for new therapeutic options. One recent promising route is the application of loco-regional therapies, particularly the pancreatic arterial infusion (PAI) of chemotherapy, delivering remarkably higher concentrations of antineoplastic agents to the tumor site than systemic administration and limiting adverse events (AEs).This type of therapeutic approach has already been successfully evaluated in various solid tumors, specifically in primary and metastatic liver cancers [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. As for advanced PC, only a few clinical trials have investigated the safety and efficacy of PAI with promising results, especially in terms of high response rates (RRs) compared to systemic chemotherapy [ 23 ].…”

A Patient With Stage III Locally Advanced Pancreatic Adenocarcinoma Treated With Intra-Arterial Infusion FOLFIRINOX: Impressive Tumoral Response and Death due to Legionella pneumophila Infection: A Unique Case Report

“…From a general point of view, the main clinical studies of IA infusion chemotherapy have been performed for liver metastases from colorectal and breast cancers, and primary hepatobiliary tumors ( 14 , 25 , 26 ). These clinical reports have indicated that IA infusion chemotherapy is safe and can provide very encouraging results.…”