Capecitabine

Capecitabine is an anticancer medicine taken by mouth. It is used to treat several types of cancer. Once it is in the body, it is changed into fluorouracil, which is an antimetabolite, and it is this drug that slows the growth of tumour tissue by blocking DNA synthesis.

Capecitabine is a prodrug. This means it has little cytotoxic effect until it is converted. The conversion is carried out by thymidine phosphorylase, an enzyme that is found in higher amounts in many tumours than in normal tissue or in the blood plasma. So the active drug is made mostly where the tumour is, which is why the effect is concentrated there.

Fluorouracil is then broken down further, inside both normal and tumour cells, into two active metabolites: 5-fluoro-2'-deoxyuridine 5-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). They damage cells in two different ways.

The first way involves FdUMP. It binds to thymidylate synthase (TS), together with the folate cofactor N5-10 methylenetetrahydrofolate, and forms a covalently bound ternary complex. This stops thymidylate from being made from 2-deoxyuridylate. Thymidylate is needed to make thymidine triphosphate, which DNA cannot be built without, so when it runs short, cell division is blocked.

The second way involves FUTP. During the making of RNA, enzymes in the cell nucleus can take FUTP by mistake in place of uridine triphosphate (UTP). This faulty RNA disrupts RNA processing and protein synthesis.