New drugs in the treatment of colorectal carcinoma

Treatment with 5-fluorouracil (5-FU) plus leucovorin has been the unofficial standard therapy for patients with colorectal carcinoma (CRC) for more than a decade; however, the optimal dose and schedule remain a matter of debate. Recently several new drugs have shown activity in this disease. These include irinotecan (CPT-11); oxaliplatin; the thymidylate synthase inhibitors raltitrexed, uracil/tegafur (UFT), capecitabine, and S-1; the biochemical modulators trimetrexate and 5-ethynyluracil; and the monoclonal antibody 17-1A. The results of clinical trials with these and other new agents, as well as their current status and main characteristics, were reviewed. Several of these agents, some with a novel mechanism of action, show promising activity in CRC. In combination with 5-FU and leucovorin, trimetrexate showed encouraging response rates in Phase II studies. Other interesting agents include capecitabine, UFT, and S-1. The biochemical modulator 5-ethynyluracil may allow the oral administration of 5-FU; however, results of Phase II clinical trials are not yet available. CPT-11 is in the most advanced stage of development and, based on consistent data generated in extensive Phase II studies, currently appears to be a reasonable choice for 5-FU-resistant or refractory disease. Another promising agent is oxaliplatin, which showed activity as first-line and second-line treatment. Several new agents have shown promise in the treatment of CRC, and changes in the standard treatment of advanced or high risk CRC appear likely in the near future