Xeloda in colorectal cancer

Xeloda (capecitabine) is a rationally designed, oral pro-drug of 5-fluorouracil (5-FU). It is rapidly and almost completely absorbed in the upper gastrointestinal tract. It is then catabolised in a three-enzyme system, the last step being catalysed by thymidine phosphorylase, which is upregulated in many human cancers. Clinical pharmacology studies have confirmed that this preferential activation actually occurs in human colorectal cancer. Phase I and II trials were performed in colorectal cancer to define the optimal dose and schedule of capecitabine. In two large scale phase III studies this agent has been shown to be at least as effective as a standard regimen of bolus 5-FU and leucovorin (Mayo regimen). Response was superior in the capecitabine arms of these studies with equivalence of progression-free and overall survival. In addition the oral regimen was associated with significantly less toxicity. It seems likely that this agent will replace intravenous 5-FU in the therapy of colorectal cancer and possibly in other cancers.