Phase II study of irinotecan, leucovorin, 5-fluorouracil and tegafur/uracil for metastatic colorectal cancer.

Irinotecan combined with continuous-infusion 5-fluorouracil (5FU) has been shown to be an effective and tolerable regimen in the treatment of metastatic colorectal cancer (MCRC). Tegafur/uracil (UFT) during 5FU infusion enhances plasma 5FU concentration, mimics continuous 5FU infusion and delivers the drug to target tumor cells. We conducted a phase II trial of four-agent combined therapy for MCRC, giving patients (pts) intravenous irinotecan (30 mg/m2 on day 1), leucovorin (LV, 200 mg/m2 on day 1 and 2), 5FU (300 mg/m2 on day 1 and 2), and UFT (400 mg/day for 14 days). The main endpoint was the objective tumor response rate. Sixteen pts with a good performance status were enrolled from February 2001 to May 2002. The response rate was 19% (3 partial responses), and 13 pts had stable disease. The median time to progression was 5.2 months, and the median survival time was 20.2 months. Considering the low toxicity and reasonable cost, this regimen deserves further investigation.

Adaptive cytoprotection against acetic acid induced colonic injury in rats.

BACKGROUND AND AIMS: The phenomenon of prostaglandin dependent adaptive cytoprotection has been well established in the stomach and duodenum but not in the colon. This study investigated whether it also occurs in the colon. METHODS: Fisher rats received intracolonic administration (0.5 ml) of saline or acetic acid at low concentrations (0.01-5%) followed by high concentration (25%) at various intervals (10-720 min). The distal colon was removed 2 h after acetic acid (25%), and colonic injury was assessed macroscopically and histologically and scored. Indomethacin (5 mg/kg) or N(G)-nitro-L-arginine methyl ester (10 mg/kg) was injected intraperitoneally 1 h or 30 min before pretreatment with 1% acetic acid. RESULTS: Acetic acid (25%) administered into the colon induced 11.6+/-0.2 macroscopic scores and 10.0+/-0.4 histological scores in saline-pretreated rats, which were reduced to 0.3+/-0.2 and 1.8+/-0.5 by acetic acid (1%) pretreatment, respectively. The protective effect assessed macroscopically and histologically was dose related (0.01-1% acetic acid) and long lasting (maximal at 30 min and lasting up to 6 h). Indomethacin abolished the colonic adaptive cytoprotection while nitric oxide synthase inhibitor had no effect. CONCLUSIONS: These data show that prostaglandin dependent adaptive protection is induced by exposure of the colon to low concentrations of acetic acid, suggesting that endogenous defense mechanisms are increased in the colon by mild irritants.