What is Xeloda (capecitabine) used for and what are its side effects?

Xeloda (Capecitabine): Indications and Side Effects

Xeloda (capecitabine) is an oral fluoropyrimidine chemotherapy agent used primarily for treating colorectal cancer and breast cancer, with its most characteristic side effect being hand-foot syndrome, which affects up to 73% of patients. 1

What Xeloda Is Used For

Capecitabine is an orally administered prodrug that converts to 5-fluorouracil (5-FU) preferentially within tumor cells, allowing for targeted chemotherapy delivery. 2

FDA-Approved Indications

Colorectal Cancer:

• First-line treatment for metastatic colorectal cancer when single-agent fluoropyrimidine therapy is preferred 3, 4
• Adjuvant therapy for stage II-III colon cancer, with capecitabine monotherapy being the preferred fluoropyrimidine regimen 5
• Used in combination regimens such as CAPEOX (capecitabine plus oxaliplatin) for adjuvant treatment, typically 1,000 mg/m² orally twice daily for days 1-14 of each 3-week cycle 5

Breast Cancer:

• In combination with docetaxel for metastatic breast cancer after failure of anthracycline-based chemotherapy 3, 4
• As monotherapy for metastatic breast cancer resistant to both paclitaxel and anthracycline therapy 3, 6

Gastric/Gastroesophageal Cancer:

• As effective as intravenous 5-FU in advanced gastric cancer, with superior overall survival (10.5 vs 9.3 months) when combined with cisplatin 5

Anal Cancer:

• Acceptable alternative to infusional 5-FU when combined with mitomycin and radiation therapy 5

Side Effects of Xeloda

Most Common Side Effects (From FDA Label)

Gastrointestinal Effects:

• Diarrhea (very common, particularly concerning if 4+ additional bowel movements per day) 3
• Nausea and vomiting 3
• Mouth and throat sores (stomatitis) 3
• Abdominal pain 3
• Constipation and loss of appetite 3
• Dehydration (more common in patients age 80 and older) 3

Dermatologic Effects:

• Hand-foot syndrome (palmar-plantar erythrodysesthesia): The most characteristic adverse effect, occurring in up to 73% of patients with 11% experiencing grade 3 severity 1
  • Manifests as tingling, numbness, pain, swelling, or redness of hands/feet that can prevent normal activity 3
  • Higher incidence (25.2%) when combined with docetaxel 1
• Rash, dry or itchy skin, skin discoloration 3
• Nail problems and hair loss 3

Systemic Effects:

• Fatigue and weakness 3
• Dizziness and headache 3
• Fever 3
• Pain (chest, back, joint, muscle) 3
• Trouble sleeping and taste problems 3

Serious Side Effects Requiring Immediate Medical Attention

Hematologic Toxicity:

• Thrombocytopenia, especially when combined with other agents 1
• Significantly lower incidence of grade 3/4 myelotoxicity compared to infusional 5-FU 2, 4

Special Population Risks:

• Patients over 65 years have 34% risk of grade 3 or higher toxicity, including treatment-related deaths 1
• Patients with DPD (dihydropyrimidine dehydrogenase) deficiency (3-5% of population) may experience potentially life-threatening toxicity 1, 3

Drug Interactions:

• Critical: Increases effect of warfarin (Coumadin), requiring more frequent INR monitoring and potential dose adjustments 3, 4
• Increases phenytoin (Dilantin) levels, requiring more frequent blood level monitoring 3

When to Stop Treatment Immediately

The FDA label specifies stopping capecitabine and contacting your doctor immediately if: 3

• Diarrhea: 4+ additional bowel movements per day beyond baseline or any nighttime diarrhea
• Vomiting: More than once in 24 hours
• Severe nausea: Marked loss of appetite with significantly reduced food intake
• Stomatitis: Pain, redness, swelling, or sores in mouth
• Hand-foot syndrome: Pain, swelling, or redness preventing normal activity
• Fever/infection: Temperature ≥100.5°F or signs of infection

Dose Modifications for Toxicity

For grade 1 toxicity, continue treatment with close monitoring. 1 For grade 2-4 toxicity, dose interruption or reduction is typically required, with most side effects improving within 2-3 days after stopping the medication. 3

Renal Considerations

Capecitabine requires dose adjustment in renal insufficiency since elimination is primarily renal—75% dose reduction recommended for creatinine clearance 30-50 mL/min, and the drug is contraindicated if CrCl <30 mL/min. 1, 4

Contraindications

Do not take Xeloda if you: 3

• Are nursing (drug passes into breast milk)
• Are allergic to capecitabine or 5-fluorouracil
• Have been diagnosed with DPD enzyme deficiency
• Are pregnant (may harm unborn child—use effective birth control during treatment)