Capecitabine Dosing and Treatment Regimens
The FDA-approved dose of capecitabine is 1250 mg/m² orally twice daily for 14 days followed by a 7-day rest period in 3-week cycles, though North American patients frequently require dose reduction to 850-1000 mg/m² twice daily due to increased toxicity compared to European patients. 1, 2
Standard Dosing by Indication
Colorectal Cancer
- Monotherapy: 850-1250 mg/m² orally twice daily for days 1-14, repeated every 3 weeks 2, 1
- Adjuvant Dukes' C colon cancer: 1250 mg/m² twice daily for 2 weeks followed by 1-week rest for 8 cycles (total 24 weeks/6 months) 1
- CapeOX regimen: Capecitabine 850-1000 mg/m² twice daily for 14 days + oxaliplatin 130 mg/m² IV day 1, repeated every 3 weeks 2
Breast Cancer
- Monotherapy: 1000-1250 mg/m² orally twice daily for days 1-14, repeated every 21 days 2
- With docetaxel: Capecitabine 950-1250 mg/m² twice daily for 14 days + docetaxel 75 mg/m² IV day 1, repeated every 21 days 2, 1
- With ixabepilone: Capecitabine 2000 mg/m² daily for days 1-14 + ixabepilone 40 mg/m² IV day 1, repeated every 21 days 2
Critical Geographic Dosing Considerations
North American patients experience significantly greater toxicity with capecitabine than European patients and typically require lower starting doses. 2, 3
- European standard: 1000 mg/m² twice daily 2
- North American recommendation: 850-1000 mg/m² twice daily 2, 3
- The relative efficacy of lower starting doses has not been addressed in large-scale randomized trials, but clinical experience supports this approach 2
Administration Guidelines
- Tablets must be swallowed with water within 30 minutes after a meal 1
- Doses should be divided equally between morning and evening, typically separated by 12 hours 1, 4
- Once dose is reduced due to toxicity, it should not be increased at a later time 1
Dose Modifications for Toxicity
Grade 2 Toxicity
- During treatment cycle: Interrupt capecitabine until resolved to grade 0-1, then resume at same dose during the cycle 1
- Persisting at next cycle: Delay treatment until resolved to grade 0-1, then continue at 100% of original dose 1
Grade 3 Toxicity
- During treatment cycle: Interrupt capecitabine until resolved to grade 0-1, then resume at 75% of original dose 1
- Persisting at next cycle: Delay treatment until resolved to grade 0-1, then continue subsequent cycles at 75% of original dose 1
Grade 4 Toxicity
- Discontinue treatment permanently or reduce to 50% of original dose after resolution 1
Renal Impairment Adjustments
- CrCl 30-50 mL/min: Reduce dose to 75% (approximately 950 mg/m² twice daily) 1, 4
- CrCl <30 mL/min: Contraindicated 1, 4
Common Dose-Limiting Toxicities
The most frequent adverse effects requiring dose modification include:
- Hand-foot syndrome (palmar-plantar erythrodysesthesia) 4, 5, 6
- Diarrhea 4, 5, 6
- Hyperbilirubinemia 4
- Nausea and fatigue 4, 5
Clinical experience demonstrates that doses of 1000 mg/m² twice daily provide better tolerability with maintained efficacy compared to the FDA-approved 1250 mg/m² dose. 5, 7
Important Drug Interactions
- Warfarin: Capecitabine increases INR; warfarin dose reduction may be necessary with close monitoring 1, 4
- Phenytoin: Capecitabine increases serum phenytoin levels; phenytoin dose reduction may be required 1, 4
Combination Therapy Considerations
With Bevacizumab
- Capecitabine 850-1000 mg/m² twice daily for 14 days + bevacizumab 7.5 mg/kg IV day 1 (when combined with oxaliplatin) or 5 mg/kg IV weekly, repeated every 3 weeks 2
- Increased risk of arterial thrombotic events, especially in patients ≥65 years 8
Duration of Oxaliplatin in CapeOX
- Discontinue oxaliplatin after 3-4 months or sooner if neurotoxicity ≥grade 2 develops 8
- Continue capecitabine and bevacizumab (if used) until disease progression 8
- Oxaliplatin may be reintroduced if discontinued for neurotoxicity rather than disease progression 8
Common Pitfalls to Avoid
- Do not use capecitabine as salvage therapy after failure on a fluoropyrimidine-containing regimen—this has been shown to be ineffective 2
- Do not start all North American patients at the European standard dose of 1000 mg/m² without close monitoring in the first cycle 2
- Do not combine multiple biologic agents (anti-EGFR + anti-VEGF) with capecitabine-based chemotherapy 2
- Do not continue oxaliplatin beyond 3-4 months if significant neurotoxicity develops 8