Capecitabine

Capecitabine is indicated for

• adjuvant treatment of people with Stage III colon cancer as a single agent or as a component of a combination chemotherapy regimen;^[8]
• perioperative treatment of adults with locally advanced rectal cancer as a component of chemoradiotherapy;^[8]
• treatment of people with unresectable or metastatic colorectal cancer as a single agent or as a component of a combination chemotherapy regimen;^[8]
• treatment of people with advanced or metastatic breast cancer as a single agent if an anthracycline- or taxane-containing chemotherapy is not indicated;^[8]
• treatment of people with advanced or metastatic breast cancer in combination with docetaxel after disease progression on prior anthracycline-containing chemotherapy;^[8]
• treatment of adults with unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer as a component of a combination chemotherapy regimen;^[8]
• treatment of adults with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease as a component of a combination regimen;^[8]
• adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy regimen.^[8]

Adverse effects by frequency:^{[9][10][11][12]}

Very common (>10% frequency)

Notes on adverse effects:

Contraindications include:^[11]

• History of hypersensitivity to fluorouracil, capecitabine or any of its excipients
• DPD deficiency (see Pharmacogenetics)
• Pregnancy and lactation
• Severe leucopenia, neutropenia, or thrombocytopenia
• Severe hepatic impairment or severe renal impairment
• Treatment with sorivudine or its chemically related analogues, such as brivudine

Drugs it is known to interact with include:^[11]

• Sorivudine or its analogues, such as, brivudine.
• CYP2C9 substrates, including, warfarin and other coumarin-derivatives anticoagulants
• Phenytoin, as it increases the plasma concentrations of phenytoin.
• Calcium folinate may enhance the therapeutic effects of capecitabine by means of synergising with its metabolite, 5-FU. It may also induce more severe diarrhoea by means of this synergy.^[14]

The dihydropyrimidine dehydrogenase (DPD) enzyme is responsible for the detoxifying metabolism of fluoropyrimidines, a class of drugs that includes capecitabine, 5-fluorouracil and tegafur.^[5] Genetic variations within the DPD gene (DPYD) can lead to reduced or absent DPD activity, and individuals who are heterozygousorhomozygous for these variations may have partial or complete DPD deficiency; an estimated 0.2% of individuals have complete DPD deficiency.^[5][15] Those with partial or complete DPD deficiency have a significantly increased risk of severe or even fatal drug toxicities when treated with fluoropyrimidines; examples of toxicities include myelosuppression, neurotoxicity and hand-foot syndrome.^[5][15]

Click on genes, proteins and metabolites below to link to respective articles.^{[§ 1]}

Capecitabine is metabolised to 5-FU which in turn is a thymidylate synthase inhibitor, hence inhibiting the synthesis of thymidine monophosphate (ThMP), the active form of thymidine which is required for the de novo synthesis of DNA.^[16]

One of the brand names is Xeloda, marketed by Genentech.

Others include Xitabin, Capcibin, Kapetral and Pecaset by Eurolab.

• Dean L (2016). "Capecitabine Therapy and DPYD Genotype". In Pratt VM, McLeod HL, Rubinstein WS, et al. (eds.). Medical Genetics Summaries. National Center for Biotechnology Information (NCBI). PMID 28520372. Bookshelf ID: NBK385155.