New drugs in the treatment of colorectal carcinoma

Abstract

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. Cancer 1998;83:679‐689. © 1998 American Cancer Society.

The Consequences of Diarrhea Occurring During Chemotherapy for Colorectal Cancer: A Retrospective Study

“…However, these adjuvant treatments can frequently be more aggressive regimens to increase the potential of further remission or cure, and they also carry increased risks for development of CID [1]. Researchers continue to investigate chemotherapy regimens and dosing schedules that would provide increased efficacy and decreased toxicity in treating advanced colorectal cancer, and a variety of drugs are currently being tested in experimental clinical trials (e.g., capecitabine, oxaliplatin, and raltitrexed) [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17].…”

Enzyme-Catalyzed Activation of Anticancer Prodrugs

“…This prodrug is sequentially activated into 5-FU by three enzymes, i.e., carboxylesterase, cytidine deaminase, and thymidine phosphorylase. Capecitabine is a promising 5-FU prodrug that is more effective against murine and human tumors than 5-FU, and clinical trials are in progress (Punt, 1998). In addition to 5-FU prodrugs, several doxorubicin prodrugs have been developed, i.e., N-(4-phosphonooxy)-phenylacetyl)doxorubicin that is activated by alkaline phosphatase (Vrudhula et al, 1993a), HMR 1826 and DOX-GA3 activated by ␤-glucuronidase (Bakina et al, 1997;Leenders et al, 1999), DPO and N-(phenylacetyl) doxorubicin activated by penicillin amidase (Kerr et al, 1990), and C-DOX and PRODOX activated by ␤-lactamase (Hudyma et al, 1993;Jungheim et al, 1993) (Table 15).…”

Clinical identification of colorectal cancer patients benefiting from adjuvant uracil–tegafur (UFT): a randomized controlled trial

“…Despite the recent development of drugs such as irinotecan, oxaliplatin, bevacitumab and cetuximab, 5-Xuorouracil (5-FU) continues to have an important role in the management of advanced colorectal cancer (Douillard et al 2000;Bleiberg 1998;Punt 1998). Uracil-tegafur (UFT) is a preparation combining uracil and tegafur in a Wxed molar ratio of 4:1 .…”