Development of treatment for advanced colorectal cancer: infusional 5-FU and the role of new agents.

Despite the fact that it was first introduced as a cancer treatment over 30 years ago, the mainstay cytotoxic agent for the treatment of metastatic colonic cancer is still 5-fluorouracil (5-FU). However, even after all this time, there is still no standard schedule for 5-FU administration which is recognised by the oncology profession. Bolus infusion remains the most popular choice, but recent investigations into short- and long-term continuous infusion schedules of 5-FU have offered advantages in terms of objective response rates and toxicity. In addition, combination infusion regimens (whereby the effectiveness of 5-FU is modulated through its co-administration with other agents or chronomodulation) are becoming accepted, although, once again, there is no recognised standard treatment regimen. This paper reviews the data from those non-comparative studies in which 5-FU has been administered as monotherapy, and relates this to data from studies of 5-FU co-administration with folinic acid and interferon. Data from other treatment regimens, which include topoisomerase I inhibitor schedules and chronomodulation of 5-FU with oxaliplatin, are presented. The advantages and disadvantages of these different regimens based upon these non-comparative data, and their position relative to standard therapies, are discussed. The likely developments with regard to the clinical and health-economic requirements for newer treatment are outlined.