HEPATIC ARTERIAL CHEMOTHERAPY FOR METASTATIC COLORECTAL-CARCINOMA

In this review, the rationale of regional chemotherapy for treatment o f hepatic metastases in advanced colorectal carcinoma is discussed. Ph armacokinetic principles and early clinical experience of hepatic arte rial drug administration are summarised. The regional advantage of flu oropyrimidine compounds in this setting is well established, and recen t evidence suggests that 5-fluorouracil (5-FU) is more efficacious tha n the analogue 5-fluoro-2'-deoxyuridine (FUDR). However, while signifi cantly higher clinical response rates can be achieved with hepatic art erial infusion (HAI) chemotherapy compared with conventional intraveno us drug administration, patient survival benefit is not significantly different. Several novel approaches to overcome the limitations of HAI therapy are currently being explored. These include concomitant use o f biodegradable microspheres, which both dow tumour blood flow and enh ance tumour drug uptake, and use of vasoactive agents to redistribute arterial blood flow towards tumours. In addition, novel chemotherapeut ic agents which exploit unique biological characteristics of hepatic t umours are entering clinical trial.