Advances in the treatment of metastatic colorectal cancer

Colorectal cancer represents the third leading cause of cancer mortality in the United States. During the past four decades, 5-fluorouracil (5-FU) has served as the cornerstone of therapy for individuals with advanced colorectal cancer (ACRC). Despite numerous attempts at maximizing efficacy of 5-FU through biochemical modulation, a significant benefit in terms of survival has never been realized. The recent emergence of novel chemotherapeutic drugs employing different mechanisms of action than 5-FU has led to the incorporation of irinotecan (CPT-11) with 5-FU/leucovorin as the new standard first-line regimen for future trials. This review outlines emerging data utilizing oral fluoropyrimidines and other new agents including oxaliplatin, raltitrexed, and eniluracil. Randomized clinical trials are currently underway in an effort to define optimal combination chemotherapy regimens, scheduling of agents, duration of therapy, and choice of therapy using a variety of prognostic molecular markers.