What is the recommended dosage and administration of Xeloda (capecitabine) for cancer treatment?

Xeloda (Capecitabine) Dosing and Administration for Cancer Treatment

The standard FDA-approved dose of Xeloda is 1,250 mg/m² orally twice daily (morning and evening) for 14 days followed by a 7-day rest period, repeated every 3 weeks, with tablets taken within 30 minutes after meals. 1

Standard Dosing Regimens by Indication

Colorectal Cancer - Adjuvant Treatment

• Capecitabine monotherapy: 1,250 mg/m² orally twice daily, days 1-14, repeated every 3 weeks for 8 cycles (total 6 months) 2, 1
• CAPEOX combination (preferred for adjuvant therapy):
  • Oxaliplatin 130 mg/m² IV over 2 hours, day 1
  • Capecitabine 1,000 mg/m² orally twice daily, days 1-14
  • Repeat every 3 weeks for 8 cycles 2
• High-risk stage II and low-risk stage III patients (T1-3N1) may receive only 3 months of CAPEOX 2

Colorectal Cancer - Metastatic/Palliative Treatment

• CapIRI regimen:

  • Irinotecan 180 mg/m² IV, day 1
  • Capecitabine 1,000 mg/m² orally twice daily, days 1-7
  • Repeat every 2 weeks 2

• mXELIRI regimen:

  • Irinotecan 200 mg/m² IV, day 1
  • Capecitabine 800 mg/m² orally twice daily, days 1-14
  • Repeat every 3 weeks 2

Rectal Cancer - Consolidation Therapy

• CAPOX consolidation (after chemoradiotherapy):
  • Oxaliplatin 130 mg/m² IV over 2 hours, day 1
  • Capecitabine 1,000 mg/m² orally twice daily, days 1-14
  • Repeat every 3 weeks for 5 cycles (induction) or 8 cycles (consolidation) 3

Breast Cancer

• Monotherapy: 1,250 mg/m² orally twice daily for 14 days, followed by 7-day rest, repeated every 3 weeks 1
• With docetaxel: 1,250 mg/m² orally twice daily for 14 days, followed by 7-day rest, combined with docetaxel 75 mg/m² IV every 3 weeks 1

Dose Calculation by Body Surface Area

The FDA label provides specific tablet counts based on BSA for the 1,250 mg/m² twice daily dose 1:

• BSA 1.26-1.37 m²: 3,300 mg total daily (1 × 150 mg + 3 × 500 mg tablets per dose)
• BSA 1.52-1.65 m²: 4,000 mg total daily (4 × 500 mg tablets per dose)
• BSA 1.78-1.91 m²: 4,600 mg total daily (2 × 150 mg + 4 × 500 mg tablets per dose)
• BSA 1.92-2.05 m²: 5,000 mg total daily (5 × 500 mg tablets per dose)

For a patient with BSA 1.8 m², the dose would be 1,800 mg twice daily (total 3,600 mg/day) 4

Critical Dosing Considerations

North American vs. European Populations

North American patients experience greater toxicity with capecitabine than European patients, warranting a starting dose of 1,000 mg/m² twice daily rather than 1,250 mg/m² in combination regimens. 4 This is particularly important for CAPEOX regimens where the Chinese Society of Clinical Oncology recommends 1,000 mg/m² twice daily 2, while the FDA label states 1,250 mg/m² 1.

Renal Impairment

• CrCl 30-50 mL/min: Reduce dose to 75% (approximately 950 mg/m² twice daily) 1, 5
• CrCl <30 mL/min: Contraindicated per FDA label 1, 5
• However, retrospective data suggests capecitabine can be used cautiously in severe renal impairment (GFR <30 mL/min) and even hemodialysis patients with starting doses of 250-1,000 mg/m² and close monitoring, though this is off-label 6

Timing with Meals

Capecitabine must be taken within 30 minutes after a meal to optimize absorption and reduce gastrointestinal toxicity. 1

Dose Modifications for Toxicity

Grade 2 Toxicity

• During 14-day treatment period: Interrupt treatment until resolved to grade 0-1, then resume at same dose during the cycle 1
• Persisting at next cycle: Delay treatment until resolved, then continue at 100% dose 1

Grade 3 Toxicity

• During treatment: Interrupt until resolved to grade 0-1, then resume at 75% of original dose 1
• Persisting at next cycle: Delay until resolved, then continue subsequent cycles at 75% dose 1

Grade 4 Toxicity

• Discontinue treatment permanently 1

Once dose is reduced, it should never be re-escalated. 1

Duration of Therapy

Adjuvant Setting

• Colon cancer: 6 months total (8 cycles of 3-week regimen) 2, 1
• Rectal cancer consolidation: 3-6 months depending on regimen 3
• Adjuvant chemotherapy should start within 3 weeks and no later than 2 months postoperatively 2

Metastatic Setting

• Continue until disease progression or unacceptable toxicity 1
• For CAPEOX with bevacizumab, consider discontinuing oxaliplatin after 3-4 months if grade ≥2 neurotoxicity develops, while continuing capecitabine and bevacizumab 7, 4

Common Pitfalls and Monitoring

Hand-Foot Syndrome

The most characteristic toxicity of capecitabine, occurring more frequently than with IV 5-FU/LV 5, 8. Dose reduction at earliest signs is critical to prevent progression to grade 3 4.

Drug Interactions

• Warfarin: Capecitabine increases INR; monitor closely and reduce warfarin dose as needed 1, 5
• Phenytoin: Capecitabine increases phenytoin levels; reduce phenytoin dose and monitor levels 1, 5

Monitoring Parameters

• Complete blood counts before each cycle 3
• Liver and renal function before each cycle 3
• Hand-foot syndrome assessment at each visit 4
• Peripheral neuropathy when combined with oxaliplatin 3, 4

Contraindications in Combination Therapy

Never combine cytotoxics with both anti-EGFR and anti-VEGF agents simultaneously. 4 Choose either cetuximab/panitumumab (for RAS wild-type) or bevacizumab (for RAS mutant or when anti-EGFR not appropriate) 7.