NEW DRUGS IN THE TREATMENT OF COLORECTAL-CARCINOMA

BACKGROUND. Treatment with 5-fluorouracil (5-FU) plus leucovorin has b een the unofficial standard therapy for patients with colorectal carci noma (CRC) for more than a decade; however, the optimal dose and sched ule remain a matter of debate. Recently several new drugs have shown a ctivity in this disease. These include irinotecan (CPT-11); oxaliplati n; the thymidylate synthase inhibitors raltitrexed, uracil/tegafur (UF T), capecitabine, and S-1; the biochemical modulators trimetrexate and 5-ethynyluracil; and the monoclonal antibody 17-1A. METHODS. The resu lts of clinical trials with these and other new agents, as well as the ir current status and main characteristics, were reviewed. RESULTS. Se veral of these agents, some with a novel mechanism of action, show pro mising activity in CRC. In combination with 5-FU and leucovorin, trime trexate showed encouraging response rates in Phase II studies. Other i nteresting agents include capecitabine, UFT, and S-l. The biochemical modulator 5-ethynyluracil may allow the oral administration of 5-FU; h owever, results of Phase II clinical trials are not yet available. CPT -11 is in the most advanced stage of development and, based on consist ent data generated in extensive Phase II studies, currently appears to be a reasonable choice for 5-FU-resistant or refractory disease. Anot her promising agent is oxaliplatin, which showed activity as first-lin e and second-line treatment. CONCLUSIONS. Several new agents have show n promise in the treatment of CRC, and changes in the standard treatme nt of advanced or high risk CRC appear likely in the near future. Canc er 1998;83:679-89. (C) 1998 American Cancer Society.