Systemic treatment of advanced colorectal cancer: Incorporating new agents into the therapeutic strategy

Abstract

Abstract Despite advances in the adjuvant therapy of colorectal cancer, treatment of advanced colorectal cancer has shown little progress until recently. Fluoropyrimidines, and specifically 5-fluorouracil (5FU), have been the mainstay of therapy, but with median survivals of only 10 to 11 months. More aggressive infusional regimens of 5FU or 5FU regimens modulated with agents such as the reduced folate, leucovorin, resulted in a modest improvement in survival. However, in recent years, 2 new cytotoxic drugs, irinotecan (CPT-11) and oxaliplatin, have been introduced into the clinic and are highly active. Irinotecan was approved by the Food & Drug Administration (FDA) as first-line therapy in combination with 5FU and leucovorin for the treatment of advanced colorectal cancer. In 2 trials, median survivals of up to 17 months were achieved. However, toxicities have been formidable, with excess mortality observed in some trials. Oxaliplatin, largely developed in European trials, has only recently been introduced to the United States. Preliminary results suggest that oxaliplatin-containing regimens are associated with improved response rates, time to progression, and overall survivals of up to 19 months. Toxicities appear to be acceptable. Further studies will determine how best to combine these 3 active agents in the treatment of advanced colon cancer. Copyright 2002, Elsevier Science (USA). All rights reserved.