Hepatic arterial infusion in colorectal carcinoma: is anatomical targeting still relevant in an era of molecularly targeted therapy?

BACKGROUND Historically, metastatic colorectal carcinoma was regarded as a tumor that is relatively resistant to cytotoxic-agents. Due to the limited number of treatment options, methods have been investigated to enhance selectivity. One method for enhancing selectivity is anatomical targeting, including hepatic arterial infusion (HAI). METHODS A comprehensive review of the literature. RESULTS Early studies with HAI used fluoropyrimidines, 5-fluorouracil or floxuridine. Several randomized trials comparing the HAI of fluoropyrimidines with systemic administration of fluoropyrimidines or best supportive care that were conducted in the 1980s and early 1990s demonstrated a superior objective response rate, but usually not a prolongation of survival in patients treated with HAI. The current standard of first line systemic chemotherapy of metastatic colorectal carcinoma is combination chemotherapy (fluoropyrimidines, oxaliplatin and/or irinotecan) administered with targeted agents. A number of trials have reported promising activity of the HAI of oxaliplatin and/or irinotecan with fluoropyrimidines, but only pilot studies are available for the combination of HAI of cytotoxic agents with targeted drugs. Factors that limit the effectiveness and utilization of HAI include catheter or port system related complications, the presence of extrahepatic metastases, or increased risk of hepatic toxicity. CONCLUSIONS HAI could be considered in clinical practice in different settings, including patients after liver resection, as second line therapy in patients failing standard front line regimens and as neodjuvant therapy to convert to resectability. Future studies should specifically concentrate on identifying regimens that would result in increased cure rates in patients with isolated hepatic metastases. For this reason, exploiting anatomical selectivity may still be a useful approach, even in the era of targeted therapy.