Colorectal cancer: Chemotherapy treatment overview

Fluorouracil (5-FU) has remained the standard therapy for the treatment of advanced colorectal cancer for over 40 yeats. Unfortunately, only a minorit y of patients experience objective clinical response. Discussed herein are attempts to improve on the activity of 5-FU by biochemically modulating ifs 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 plu s oral 5-FU) provide the convenience of oral delivery with a marked reducti on in febrile neutropenia and mucositis. Recent randomized trials with thes e agents have demonstrated therapeutic activity that is comparable with int ravenous schedules of 5-FU plus leucovorin. Compared to 5-FU, both oxalipla tin and irinotecan have uniquely different mechanisms of action and have de monstrated 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/leuc ovorin improves response rates and time to progression compared to 5-FU/leu covorin alone. Combination chemotherapy regimens with these novel agents ar e rapidly being introduced into the adjuvant setting.