Use of capecitabine in management of early colon cancer

Abstract

Capecitabine (Xeloda®, Roche, Basel, Switzerland) is a pro-drug of 5-fluorouracil (5-FU), and it is converted to 5-FU in the cancer cell by enzymatic degradation. The role of capecitabine in colorectal cancer has evolved in the last 15 years. In early trials in the metastatic setting, capecitabine has shown superior response rates compared with those achieved with 5-FU (Mayo Clinic regimen) (26% vs 17%), with equivalent progression-free survival and overall survival. In the adjuvant setting, the Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial demonstrated that capecitabine as a single agent led to improvement in relapse-free survival (hazard ratio: 0.86, 95% confidence interval: 0.74–0.99, P = 0.04) and was associated with significantly fewer adverse events than 5-FU plus leucovorin (LV, folinic acid). On the basis of the X-ACT trial, capecitabine was approved by the United States Food and Drug Administration, the National Institute for Clinical Excellence, and the Scottish Medicines Consortium as monotherapy for the adjuvant treatment of stage III colon cancer. The next step was to incorporate capecitabine into combination therapy. The XELOXA trial studied the combination of capecitabine and oxaliplatin (XELOX) vs 5-FU/LV and demonstrated 5-year disease-free survival of 66% for XELOX, compared with 60% for 5-FU/LV. The toxicity profile was also quite comparable in the two arms. So both the single agent use of capecitabine as well as in combination with oxaliplatin can be considered as part of the standard of care in management of early colon cancer in appropriately selected patient groups.

Pharmacogenetic variants in the DPYD, TYMS, CDA and MTHFR genes are clinically significant predictors of fluoropyrimidine toxicity

“…Capecitabine, a prodrug of 5-FU, is first hydrolysed by carboxyl esterases in the liver to form 5-fluorodeoxycytidine, which is then deaminated by cytidine deaminase (CDA) in liver and neoplastic tissue to form 5-fluorodeoxyuridine, which in turn is converted to 5-FU by thymidine phosphorylase (TP) (Hameed and Cassidy, 2011). Decreased CDA activity is predicted to lead to the accumulation of potentially toxic fluoro-cytidine metabolites.…”

Ileitis Secondary to Oral Capecitabine Treatment?

“…Capecitabine is an oral fluoropyrimidine which is preferentially converted to fluorouracil in tumour tissue, by the way of a three-step enzymatic cascade. The final stage of conversion to fluorouracil is catalysed by thymidine phosphorylase, which is appreciably more active in tumour than in healthy tissue [3]. The X-ACT trial, which compared the use of capecitabine with the MAYO regimen of bolus 5-FU/LV in patients with stage III colon cancer demonstrated similar efficacy but with reduced grade 3/4 toxicity [4].…”

Emerging new therapeutic applications of capecitabine as a first-line chemotherapeutic agent in the management of advanced carcinomas other than colorectal carcinoma

“…I read with great interest the recent article by Hameed et al in a recent issue of your journal 1. The article is very interesting.…”

“…I read with great interest the recent article by Hameed et al in a recent issue of your journal. 1 The article is very interesting. Interestingly, the past few years have seen the emergence of capecitabine as a highly potent first-line chemotherapeutic agent against advanced systemic carcinomas other than colorectal carcinoma.…”