Regional and systemic chemotherapy for colorectal metastases to the liver

The fluoropyrimidines 5-FU and FUDR are antimetabolites that have limited activity in the treatment of patients with colorectal metastases. The availability of implantable or portable drug infusion pumps has caused a renewed interest in continuous infusion therapy using these drugs for patients with colorectal metastases to the liver. While the search for new, more effective agents or combinations continues, it is reasonable to evaluate dose schedules and drug combinations that would maximize the effectiveness of these fluoropyrimidines and lower their toxicity in investigational protocols. In most series both drugs have higher response rates, less myelosuppression, but greater liver toxicity when given by continuous intraarterial infusions compared to bolus injections given intravenously. Nevertheless, there is still insufficient data to conclude that survival rates are sufficiently prolonged in patients for whom an implantable drug infusion pump has been used for regional FUDR chemotherapy. On the other hand, symptomatic patients may have sufficient palliation to constitute an identifiable group for whom this approach is justified. Results of several randomized prospective studies addressing the efficacy of regional versus systemic FUDR chemotherapy infusions will be available in the near future. If these demonstrate improved survival for patients receiving regional FUDR chemotherapy, it will be appropriate to consider this approach in selected patient settings. Until such data are available, routine use of this approach in asymptomatic patients is not warranted.