In Treatment of:
Capecitabine 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.
Potential major adverse reactions include:
1. Cardiovascular: EKG changes, myocardial infarction, angina (these may be more common in patients with pre-existing coronary artery disease)
2. 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.
3. 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.
4. Hematological: Neutropenia, anemia, and thrombocytopenia.
5. Hepatic: Hyperbilirubinemia
History of severe and unexpected reactions to fluoropyrimidine therapy; severe renal impairment; pregnancy, lactation. Hypersensitivity.
Hepatic dysfunction, bone marrow suppression, poor nutritional status, warfarin therapy. Child, elderly, prior extensive pelvic radiation or alkylating therapy. Moderate renal impairment; CBC with differential; monitor hepatic and renal function. Discontinue use if intractable diarrhoea, stomatitis, bone marrow suppression or MI develops.
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.
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.
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.