Hepatic artery chemotherapy

Primary goal of regional treatment is to deliver high concentrations total dose of chemotherapy to the tumor bed and can be safely administered by systemic infusion of the drug.

A lateral as the delivery of high-dose chemotherapy locally increasing cytotoxic effect while minimizing toxicity to uninvolved tissues.

Hepatic carcinoma has hypervascularity supplied predominantly by branches of the hepatic artery, while normal liver tissue is mostly supplied by the portal vein.

Most agents utilized have high total body clearance and showed plasma half-lives.

Cis-platinum, mitomycin-C and BCNU had a forward to a full of increasing drug exposure to the tumor using such therapy.

5-FU and FUDR had a 10 and a 400 fold increase in drug exposure, respectively when given as a hepatic artery therapy.

The liver is capable of tolerating high doses of chemotherapy because of its large functional reserve and high regenerative capacity, nevertheless infusion chemotherapy can be associated with an increased risk of hepatotoxicity.

Metastases to the liver can be treated by several types of hepatic artery treatments based on the observation that tumor cells get nearly all their nutrients from the hepatic artery, while the normal cells of the liver get about 70–80 percent of their nutrients and 50% their oxygen supply from the portal vein, and thus can survive with the hepatic artery effectively blocked.

The MRC/EORTC trial compared hepatic artery infusion chemotherapy with systemic chemotherapy with 5-FU and leucovorin and found that HAI chemotherapy had an equivalent toxicity to systemic treatment with no difference in objective response rates and median overall survival, or progression free survival in metastatic colorectal carcinoma, but the median progression free survival was 7.6 months versus 6.7 months in the systemic therapy arm (Kerry DJ).

CALGB study comparing hepatic artery infusion chemotherapy with FUDR, leucovorin and dexamethasone compared to systemic administration of 5-FU and leucovorin demonstrated a superior response with infusional treatment of 47% versus 24% for systemic therapy, and there was a 4 month overall survival benefit compared to the systemic arm at 24.4 months versus 20 months, respectively (Kennedy N).

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