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.
Schmoll
H J
HJ
Clinic for Haematology/Oncology, Martin-Luther-Universität, Halle-Wittenberg, Halle/Saale, Germany.
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D019454:Chronotherapy; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil