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

Despite the fact that it was first introduced asa cancer treatment aver 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 coadministration 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. Copyright (C) 1996 Elsevier Science Ltd