Novel agents for colorectal cancer

The compound 5-fluorouracil (5-FU) has been investigated for over four decades; research has focussed on examining various schedules and biochemical modulators in an attempt to improve its therapeutic activity in advanced colorectal cancer. Combination chemotherapy regimens have not been developed because of the lack of other active agents. Recently, several novel agents are under clinical development for advanced colorectal cancer, including irinotecan, oxaliplatin, oral fluoropyrimidines, raltitrexed, monoclonal antibody 17-1A and tumour vaccines. Both irinotecan and oxaliplatin have uniquely different mechanisms of action compared to 5-FU, and have demonstrated activity in patients whose disease has progressed with 5-FU treatment. Recent randomised trials comparing 5-FU plus leucovorin (5-FU/LV) to combinations of either irinotecan or oxaliplatin plus 5-FU/LV have demonstrated that the addition of these novel agents to 5-FU improve response rates (RRs) and time to progression (TTP). The role and acceptance of these combinations need to be defined, but are rapidly being introduced into the adjuvant therapy of colorectal cancer. Oral fluoropyrimidines (UFT plus leucovorin, capecitabine, eniluracil plus oral 5-FU, and S-1) provide the convenience of oral delivery with a marked reduction in febrile neutropenia and mucositis. To gain clinical acceptance, oral fluoropyrimidines must provide not only convenience and toxicity reduction, but also maintenance of survival advantages associated with optimal use of iv. 5-FU/LV regimens. These novel agents discussed herein provide treatment options which may allow for more individualised treatment strategies.