Symptoms And Treatment Of Cancer - 2184 Words

Capecitabine (Xeloda ®) Introduction Cancer is a disease caused by an uncontrollable increase in rate of cell division often leading to abnormal cell sizes and cell counts ultimately causing detrimental effects on cellular function especially if it has the ability to evade many treatments, as cancer has been proven to be quite adaptable. The path to curing cancer has been a long and expensive one, and while the discovery of a universal cure is currently being pursued, several treatments have been discovered and designed to treat the various subtypes of cancer . Capecitabine (Xeloda ®); a fluoropyrimidine carbamate is an orally-administered chemotherapeutic agent used in the treatment of colorectal cancer, when single-agent fluoropirimidine†¦show more content†¦Capecitabine first undergoes conversion to 5†²-deoxy-5-fluorocytidine (5’-DFCR) by carboxylesterase in the liver. 5’-DFCR then undergoes metabolic conversion to 5†²-deoxy-5-fluorouridine (5’-DFUR) by cytidine deaminase in the liver and tumor which is then converted to the cytotoxic metabolite, 5-FU by dThdPase in tumor tissues . Figure 1: Metabolic conversion of capecitabine to fluorouracil (FU). 5†²-DFCR: 5†²-deoxy-5-fluorocytidine, 5†²-DFUR: 5†²-deoxy-5-fluorouridine, 5-FU: 5-fluoro uracil, CE: carboxylesterase, CyD: cytidine deaminase . 5-fluorouracil is converted to fluorodeoxyuridine monophosphate, which binds to the enzyme thymidylate synthase; its normal substrate is uridine monophosphate. This enzyme methylates deoxyuridine monophosphate to thymidylate; precursor to thymidine triphosphate. Inhibition of thymidylate synthesis blocks DNA production and halts cell division. 5-fluorouracil is also incorporated into RNA where it obstructs RNA processing and protein synthesis. Although capecitabine is toxic to normal host cells, it is much more deadly to tumour cells because of their faster rates of metabolism and cell division . 5-FU acts as a mimic of uracil; a building block for RNA and DNA synthesis, the only difference is the extra fluorine atom (Figure 2). Although 5-fluorouracil is a potent anti-proliferative agent it used mainly for intravenous infusion therapy due to its low bioavailability and short half-life making capecitabine a more favourable drug