Quick Facts About: Capecitabine

Xeloda®

Yes, in 1998.

Capecitabine is used to treat stage III colon cancer and metastatic colorectal cancer.

*All dosages indicated here are specific to colorectal cancer treatment.

Capecitabine is administered in the form of an oral tablet.

Dosage is dependent on drug combination in the treatment regimen and is based on the patient’s body surface area (milligram per square meter, mg/m²).

Dosage is also dependent on whether capecitabine is used as a monotherapy or part of combination therapy. For stage III colon cancer adjuvant therapy, this is done over a period of six months.

Capecitabine should be taken with food, or within 30 minutes after meals.

Monotherapy:

1,250 mg/m² is administered for 14 days, and should be followed by a seven-day rest period.

Combination therapy:

800-1,000 mg/m² is administered for 14 days, and should be followed by a seven-day rest period. An alternative dosage is administering 625 mg/m² continuously.

Special precautions should be taken for patients with

• Diarrhea, dehydration or disruption in electrolyte levels
• History of cardiovascular diseases such as coronary artery disease
• Nervous system disease (e.g. neuropathy, brain metastases)
• Hyperbilirubinemia
• Diabetes
• Pre-existing abnormal levels of calcium in the blood
• Patient with low dihydropyrimidine dehydrogenase (DPD) activity
• Mild to moderate renal and/or hepatic impairment

Contraindications include:

• Known complete absence of DPD activity
• Severe leukopenia, neutropenia, or thrombocytopenia
• Severe renal and/or hepatic impairment
• Pregnancy and lactation
• Concomitant use with brivudine and oral coumarin-derivative anticoagulants

*If concomitant use with coumarin anticoagulants cannot be avoided, closely monitor INR and prothrombin time with great frequency and adjust anticoagulant dose accordingly.

The common side effects of capecitabine that patients experience include:

• Tiredness, weakness and fatigue
• Loss of appetite
• Diarrhea
• Mouth sores and ulcers
• Feeling or being sick, nausea
• Soreness, redness and peeling of skin on palms and soles of feet
• Abdominal pain and pain in other areas of the body

Capecitabine is a cytotoxic chemotherapy drug.

Capecitabine is a prodrug of 5-fluorouracil (5-FU) and is converted into 5-FU by enzymes present in the tumor cells.

Capecitabine is a nucleoside analog of deoxycytidine that gets metabolized into 5-FU by a series of enzymatic reactions. 5-FU is an antimetabolite that interferes with DNA and RNA synthesis. It inhibits the thymidylate synthase (TS) enzyme, which is necessary for the formation of thymidine, a nucleotide essential for DNA synthesis.

As a result, the cells become deficient in thymidine, leading to an accumulation of deoxyuridine monophosphate (dUMP). The excess dUMP forms an inactive complex with TS, leading to the depletion of the deoxynucleotide pool, DNA fragmentation, and eventually, cell death. Besides inhibiting TS, 5-FU also gets incorporated into RNA, disrupting its stability, and leading to impaired protein synthesis.

Additionally, 5-FU gets metabolized into active metabolites such as 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP), which forms a covalent bond with the folate cofactor and the TS enzyme, irreversibly inhibiting the enzyme's function. The result is a significant decrease in the availability of thymidine, which leads to DNA damage and apoptosis.