Clinical significance of and future perspectives for hepatic arterial infusion chemotherapy in patients with liver metastases from colorectal cancer

Abstract

The most common site of metastases in patients with colorectal cancer is the liver. Hepatic resection is considered to be the treatment of choice for liver metastasis from colorectal cancer; however, hepatic resection can be performed in only 20 or 25% of all patients. Recurrence develops in the remnant liver or other organs after hepatic resection in over half of all patients with liver-only metastasis. Hepatic arterial infusion (HAI) chemotherapy can provide relatively high concentrations of drugs to microscopic or macroscopic metastases in the liver, with less toxicity than systemic administration. Meta-analyses have shown HAI chemotherapy to have a significantly higher response rate than systemic chemotherapy and its effect on extrahepatic metastases is negligible. HAI chemotherapy provides much better local control of liver metastases from colorectal cancer than systemic chemotherapy. However, well-controlled studies are needed to elucidate the optimal treatment strategies for neoadjuvant and postoperative adjuvant chemotherapy that optimally combine HAI chemotherapy, molecular targeted agents, and systemic chemotherapy such as FOLFOX or FOLFIRI.

Hepatic arterial infusion plus systemic chemotherapy as third-line or later treatment in colorectal liver metastases

“…Several randomized trials were performed to compare HAI with SCT and best supportive care for CLMs. The results suggested that HAI was well tolerated and associated with higher response rates, although the survival benefit was limited [17,18]. Only part of studies showed a significant overall survival benefit with HAI possibly because most previous studies include a crossover arm.…”

A systematic review and meta-analysis to reappraise the role of adjuvant hepatic arterial infusion for colorectal cancer liver metastases

“…Furthermore, drugs used for HAI have a first-pass hepatic clearance effect, such as FUDR and 5-Fu. These drugs have a short half-life and are primarily metabolized in the liver, allowing extremely low drug concentrations to be maintained in the peripheral blood, thereby providing a higher exposure of chemotherapy to malignant cells and minimizing the risk of systemic adverse events [25].…”

STORE-gastrointestinal functions and gastrointestinal hormones in patients with liver failure

“…Therefore, serum GI hormone levels markedly increase in LF patients, which is consistent with the description of Feldman. [14] The possible reasons may include the decreased GI hormone inactivation by the liver following LF, the direct release of hormones into the blood due to portal hypertension, increased hormone production, and decreased hormone excretion. [15]…”