Novel chemotherapeutic agents in colorectal cancer

Colorectal cancer remains the second most common cause of cancer death in Europe. A number of new agents, with varying mechanisms of action, have been developed and are being evaluated, both as single agents and in combination. Irinotecan, a topisomerase I inhibitor, and oxaliplatin, a new platinum compound, have proven efficacy in advanced colorectal cancer resistant to 5-fluorouracil. Capecitabine and other oral fluoro-pyrimidines are also emerging as potentially effective drugs. Raltitrexed and other inhibitors of thymidylate synthase (TS) are entering clinical practice although their role has yet to be determined. The new fluoro-pyrimidines and TS inhibitors are important classes of drug which have been designed to take advantage of the knowledge of folate metabolism gained from basic clinical research. Their design features could perhaps reduce the toxicity seen with the first generation cytotoxic agents. This review will focus on these new chemotherapeutic agents in colorectal cancer with respect to their mechanisms of action, current clinical activity and their potential use both in the adjuvant and palliative settings.