Capecitabine

Capecitabine is an orally-administered chemotherapeutic agent used in the treatment of cancers. It is a prodrug that is enzymatically converted to fluorouracil (antimetabolite) in the tumor, where it inhibits DNA synthesis and slows growth of tumor tissue.

Capecitabine is a prodrug that is selectively tumor-activated to its cytotoxic moiety, fluorouracil, by thymidine phosphorylase, an enzyme found in higher concentrations in many tumors compared to normal tissues or plasma. Fluorouracil is further metabolized to two active metabolites, 5-fluoro-2'-deoxyuridine 5-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP), which interfere with DNA and RNA synthesis, causing cell injury.

• Adjuvant colon cancer (Dukes' C colon cancer)
• Metastatic colorectal cancer (first-line monotherapy)
• Metastatic breast cancer (in combination with docetaxel or as monotherapy)
• Gastric cancer (in combination with platinum-based compound)

Monotherapy (Colorectal and Breast Cancer): 1250 mg/m² twice daily (oral) for 2 weeks, followed by a 1-week rest period; 3-week cycles. Adjuvant treatment: 6 months (8 cycles) recommended.

In combination with docetaxel (Breast Cancer): 1250 mg/m² twice daily (2 weeks) + docetaxel 75 mg/m² IV (1 hour) every 3 weeks.

Gastric Cancer (with platinum-based compound): 1000 mg/m² twice daily for 14 days, followed by a 7-day rest period.

Renal impairment (CrCl 30-50 mL/min): 950 mg/m² twice daily (when starting dose is 1250 mg/m²). CrCl <30: Avoid use.

Hepatic impairment: Caution required; dose adjustment may be needed.

BSA calculation example: A person weighing 64 kg and height 1.64 m (BSA 1.7 m²) should take 4 tablets of 500 mg and 1 tablet of 150 mg twice daily.

Common side effects: Vomiting, weakness, nausea, abdominal pain, diarrhea, blisters on fingers/feet (hand-foot syndrome), fatigue, loss of appetite, stomatitis (mouth inflammation), skin rash, dry/itchy skin, fever, infection, chest pain.

Serious (rare): Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), severe diarrhea (may lead to dehydration and renal failure), cardiotoxicity, hyperbilirubinemia, bone marrow suppression (neutropenia, thrombocytopenia).

Decreased blood cells (especially white blood cells) increase susceptibility to infections; monitor CBC regularly.

• Diarrhea: Stop treatment until diarrhea resolves to Grade 1; use standard antidiarrheal treatments. Severe diarrhea may lead to dehydration and renal failure.
• Hand-foot syndrome: Interrupt treatment until symptoms resolve or decrease in intensity.
• Cardiotoxicity: Common in patients with prior history of coronary artery disease; caution required.
• Dehydration and renal failure: Stop treatment until dehydration is corrected; potential risk of acute renal failure.
• DPD deficiency: Withhold or permanently discontinue in patients with evidence of acute early-onset or unusually severe toxicity (may indicate near complete or total absence of DPD activity).
• Hematologic: Do not treat patients with neutrophil counts <1.5x10⁹/L or thrombocyte counts <100x10⁹/L.
• Coagulopathy: Monitor anticoagulant response (INR) and adjust dose accordingly (risk of bleeding).
• Do not use during pregnancy and lactation (Category D).
• Know your response before driving (may cause dizziness and tiredness).

• Severe renal impairment (CrCl <30 mL/min)
• Hypersensitivity to capecitabine
• Leukopenia, neutropenia, or thrombocytopenia
• Severe reactions to fluoropyrimidine therapy
• Complete DPD deficiency
• Pregnancy and lactation

• Anticoagulants (warfarin): Monitor INR or prothrombin time frequently; adjust anticoagulant dose as needed (risk of bleeding).
• Phenytoin: Monitor phenytoin levels; dose reduction may be needed.
• Leucovorin: Increases 5-fluorouracil concentration and may enhance toxicity.
• CYP2C9 substrates: Caution required.
• Aluminum and magnesium-containing antacids: May affect absorption.
• Food: Reduces both the rate and extent of capecitabine absorption (take within 30 minutes after a meal).