Capecitabine
Encyclopedia
Capecitabine (icon) (Xeloda, Roche) is an orally-administered chemotherapeutic agent used in the treatment of metastatic breast
and colorectal cancer
s. 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.
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.
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
and colorectal cancer
Colorectal cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....
s. Capecitabine is a prodrug
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
, that is enzymatically converted to 5-fluorouracil in the tumor, where it inhibits DNA synthesis
DNA synthesis
DNA synthesis commonly refers to:*DNA replication - DNA biosynthesis *Polymerase chain reaction - enzymatic DNA synthesis *Oligonucleotide synthesis - chemical synthesis of nucleic acids...
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 cancerColorectal cancerColorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....
Stage III Dukes' C - used as first-line monotherapy. - Metastatic colorectal cancer - used as first-line monotherapy, if appropriate.
- Metastatic breast cancerBreast cancerBreast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
- used in combination with docetaxel, after failure of anthracyclineAnthracyclineAnthracyclines are a class of drugs used in cancer chemotherapy derived from Streptomyces bacterium Streptomyces peucetius var...
-based treatment. Also as monotherapy, if the patient has failed paclitaxelPaclitaxelPaclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a U.S. National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol...
-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
National Institute for Health and Clinical Excellence
The National Institute for Health and Clinical Excellence is a special health authority of the English National Health Service , serving both English NHS and the Welsh NHS...
(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 deficiencyDihydropyrimidine dehydrogenase deficiencyDihydropyrimidine dehydrogenase deficiency is an autosomal recessivemetabolic disorder in which there is absent or significantly decreased activity of dihydropyrimidine dehydrogenase, an enzyme involved in the metabolism of uracil and thymine.Individuals with this condition may develop...
(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 infarctionMyocardial infarctionMyocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
, angina (these may be more common in patients with pre-existing coronary artery disease) - Dermatological: Hand-foot syndromePalmar plantar erythrodysesthesiaChemotherapy-induced acral erythema is reddening, swelling, numbness and desquamation on palms and soles that can occur after chemotherapy in patients with cancer. These skin changes usually are well demarcated. Acral erythema typically disappears within a few weeks after discontinuation of the...
(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: DiarrheaDiarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
(sometimes severe), nauseaNauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, stomatitisStomatitisStomatitis is an inflammation of the mucous lining of any of the structures in the mouth, which may involve the cheeks, gums, tongue, lips, throat, and roof or floor of the mouth... - Hematological: NeutropeniaNeutropeniaNeutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
, anemiaAnemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, thrombocytopeniaThrombocytopeniaThrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease... - Hepatic: Hyperbilirubinemia
Drug interactions
- May interact with warfarinWarfarinWarfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
and increase bleeding risk. - May inhibit cytochromeCytochrome P450 oxidaseThe cytochrome P450 superfamily is a large and diverse group of enzymes. The function of most CYP enzymes is to catalyze the oxidation of organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances...
CYP2C9 enzyme, and therefore increase levels of substratesSubstrate (biochemistry)In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
such as phenytoinPhenytoinPhenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
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.External links
- Xeloda.com (patient information, tools, and resources)
- OralChemo Advisor (patient information)