Colorectal cancer: chemotherapy treatment overview

Fluorouracil (5-FU) has remained the standard therapy for the treatment of advanced colorectal cancer for over 40 years. Unfortunately, only a minority of patients experience objective clinical response. Discussed herein are attempts to improve on the activity of 5-FU by biochemically modulating its action. In addition, novel agents for the treatment of advanced colorectal cancer (oral fluoropyrimidines, oxaliplatin, and irinotecan) are discussed. Oral fluoropyrimidines (UFT plus leucovorin, capecitabine, eniluracil plus oral 5-FU) provide the convenience of oral delivery with a marked reduction in febrile neutropenia and mucositis. Recent randomized trials with these agents have demonstrated therapeutic activity that is comparable with intravenous schedules of 5-FU plus leucovorin. Compared to 5-FU, both oxaliplatin and irinotecan have uniquely different mechanisms of action and have demonstrated clinical activity in patients whose disease has progressed with 5-FU treatment. Combinations of either irinotecan or oxaliplatin plus 5-FU/leucovorin have demonstrated that the addition of these agents to 5-FU/leucovorin improves response rates and time to progression compared to 5-FU/leucovorin alone. Combination chemotherapy regimens with these novel agents are rapidly being introduced into the adjuvant setting.