Novel chemotherapy agents for colorectal cancer: Oral fluoropyrimidines, oxaliplatin, and raltitrexed

Agents now under investigation for treatment of advanced colorectal cancer (CRC) include the oral fluoropyrimidines, oxaliplatin, and raltitrexed. Research efforts directed at finding agents that conveniently and effectively deliver 5-fluorouracil (5-FU) in a protracted fashion have led to the development of several oral fluoropyrimidines. These agents, which include capecitabine; tegafur and uracil plus leucovorin (UFT/LV); eniluracil plus oral 5-FU; and S-1, are convenient and less toxic than intravenous bolus 5-FU. Oxaliplatin has a uniquely different mechanism of action compared with that of 5-FU and has demonstrated activity not only in the first-line treatment setting but also in patients whose disease has progressed during or following 5-FU treatment. In the first-line setting, when oxaliplatin is combined with 5-FU plus LV, response rates and time to disease progression are remarkably improved compared with 5-FU/LV alone. Raltitrexed, a unique thymidylate synthase inhibitor, has undergone extensive phase III evaluation in CRC. The advent of these novel agents has led to development of combined chemotherapy regimens now being introduced into the adjuvant setting.