New drugs in the treatment of colorectal carcinoma

BACKGROUND: 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. METHODS: The results of clinical trials with these and other new agents, as well as their current status and main characteristics, were reviewed. RESULTS: 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. CONCLUSIONS: 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.