Capecitabine

 
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More about Capecitabine

What is/are Capecitabine?

Capecitabine (INN) /keɪpˈsaɪtəbiːn/ (Xeloda, Roche) is an orally-administered chemotherapeutic agent used in the treatment of metastatic breast and colorectal cancers. Capecitabine is a prodrug, that is enzymatically converted to 5-fluorouracil in the tumor, where it inhibits DNA synthesis and slows growth of tumor tissue. The activation of capecitabine follows a pathway with three enzymatic steps and two intermediary metabolites, 5'-deoxy-5-fluorocytidine (5'-DFCR) and 5'-deoxy-5-fluorouridine (5'-DFUR), to form 5-fluorouracil.

Indications

Capecitabine is FDA-approved for:

  • Adjuvant in colorectal cancer Stage III Dukes' C - used as first-line monotherapy.
  • Metastatic colorectal cancer - used as first-line monotherapy, if appropriate.
  • Metastatic breast cancer - used in combination with docetaxel, after failure of anthracycline-based treatment. Also as monotherapy, if the patient has failed paclitaxel-based treatment, and if anthracycline-based treatment has either failed or cannot be continued for other reasons (i.e., the patient has already received the maximum lifetime dose of an anthracycline).

In the UK, capecitabine is approved by the National Institute for Health and Clinical Excellence (NICE) for colon and colorectal cancer, and locally advanced or metastatic breast cancer. On March 29, 2007, the European Commission approved Capecitabine, in combination with platinum-based therapy (with or without epirubicin), for the first-line treatment of advanced stomach cancer.

Dose

The usual starting dose is 2,500 mg/m2/day in two divided doses, 12 hours apart. One cycle includes two weeks of treatment followed by one week without treatment. Cycles can be repeated every three weeks.

Dose adjustments

  • For mild renal dysfunction (creatinine clearance 30-50 mL/min), it is recommended to reduce dose by 25%.
  • For severe renal dysfunction (creatinine clearance <30 mL/min), treatment is not recommended.
  • There is no recommendation for hepatic dysfunction.
  • For elderly patients, lower doses may be required due to higher incidences of serious adverse reactions.
  • Patients with Dihydropyrimidine dehydrogenase deficiency (a.k.a. DPD deficiency), a pharmacogenetic syndrome affecting capecitabine detoxification process in the liver, should have their dosage tailored.

Side effects

Potential major adverse reactions include:

  • Cardiovascular: EKG changes, myocardial infarction, angina (these may be more common in patients with pre-existing coronary artery disease)
  • Dermatological: Hand-foot syndrome (numbness, tingling, pain, redness, or blistering of the palms of the hands and soles of the feet). This can lead to the disappearance of fingerprints in some patients.
  • Gastrointestinal: Diarrhea (sometimes severe), nausea, and stomatitis have occurred. Octreotide has been studied as an anti-diarrheal in cases of refractory diarrhea associated with capecitabine use.
  • Hematological: Neutropenia, anemia, and thrombocytopenia.
  • Hepatic: Hyperbilirubinemia

Drug interactions

  • May interact with warfarin and increase bleeding risk.
  • May inhibit cytochrome CYP2C9 enzyme, and therefore increase levels of substrates such as phenytoin and other substrates of CYP2C9.
  • The concomitant use of leucovorin is not recommended. Manufacturer's warning In a controlled study, leucovorin increased the toxicity of capecitabine without any apparent advantage in response rate.

Formulation

Capecitabine (as brand-name Xeloda) is available in light peach 150 mg tablets and peach 500 mg tablets.

This article uses material from the Wikipedia article Capecitabine, which is released under the Creative Commons Attribution-Share-Alike License 3.0.

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Medicine containing Xeloda

Medicine containing Capecitabine

This page uses publicly available data from the U.S. National Library of Medicine (NLM), National Institutes of Health, Department of Health and Human Services; NLM is not responsible for the page and product and does not endorse or recommend this or any other product.

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