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.

Keywords: cholangiocarcinoma; hepatic arterial infusion chemotherapy; hepatocarcinoma; implanted pump or port.

Figure 1

An example of the modification of the liver vascular network to avoid the reflux of cytotoxic drugs into the stomach and duodenum. Red circles indicate embolization by coils and spirals of non-target arterial branches, such as artery cystic, gastric arteries, accessory hepatic arteries, and pancreatic-duodenal arteries. The distal tip of the infusion catheter (big white arrow) is fixed within the gastro-duodenal (big red arrow) by means of vessel embolization. Therefore, the infusion hole of the catheter is facing the proper hepatic artery. The embolic agents are gradually released through a coaxial microcatheter (small white arrow) introduced into the lumen of the catheter up to the infusion hole (white circle). The small red arrow indicates proper hepatic artery at the origin of its branches. Scale bar equals 1 cm.

Figure 2

Final presentation of a hepatic arterial port-a-cath system implantation. Red circles indicate embolization by coils and spirals of non-target arterial branches such as artery cystic, gastric arteries, accessory hepatic arteries, and pancreatic-duodenal arteries. The small red arrow indicates the infusion catheter within the proper hepatic artery. The big red arrow corresponds to the infusion chamber of the port-a-cath system. Scale bar equals 1 cm.