What is the Capeox (capecitabine and oxaliplatin) chemotherapy regimen for colorectal cancer?

CapeOX Chemotherapy Regimen for Colorectal Cancer

CapeOX (capecitabine plus oxaliplatin) is a highly effective first-line chemotherapy regimen for metastatic colorectal cancer that is interchangeable with FOLFOX, demonstrating similar progression-free survival (8.0 vs 8.5 months) and overall survival outcomes. 1

Standard Dosing Protocol

The established CapeOX regimen consists of:

• Oxaliplatin 130 mg/m² IV infusion over 2 hours on day 1 1
• Capecitabine 1,000 mg/m² orally twice daily for 14 days (day 1 evening through day 15 morning) 1
• Repeated every 3 weeks 1

Critical Dosing Considerations for North American Patients

North American patients experience greater toxicity with capecitabine than European patients and may require lower starting doses. 1 The European standard uses 1,000 mg/m² twice daily, but dose reductions should be considered early in North American populations based on toxicity monitoring. 1

Duration and Oxaliplatin Management

Discontinue oxaliplatin after 3-4 months of therapy (or sooner if grade ≥2 neurotoxicity develops), while maintaining capecitabine ± bevacizumab until disease progression. 1 This OPTIMOX1 approach prevents cumulative neurotoxicity while maintaining disease control. 1

• Oxaliplatin may be reintroduced if previously discontinued for neurotoxicity rather than disease progression 1
• Do not use calcium/magnesium infusions to prevent oxaliplatin neurotoxicity—there is no supporting data 1

Addition of Biologic Agents

CapeOX can be combined with bevacizumab or anti-EGFR antibodies based on molecular profile:

For RAS Wild-Type, Left-Sided Tumors:

• Add panitumumab 6 mg/kg IV day 1 or cetuximab to CapeOX 2
• Anti-EGFR therapy improves response rates in this population 2
• Do not use anti-EGFR therapy for right-sided primary tumors—there is a preponderance of data showing lack of activity 1

For RAS Mutant or When Bevacizumab Preferred:

• Add bevacizumab 7.5 mg/kg IV day 1 every 3 weeks 1, 2, 3
• Increased stroke risk in patients ≥65 years 1
• May interfere with wound healing 1

Critical Pitfall to Avoid:

Never combine cytotoxics with both anti-EGFR and anti-VEGF agents—this combination is not recommended and increases toxicity without benefit. 1

Efficacy Data

CapeOX demonstrates non-inferiority to FOLFOX in metastatic colorectal cancer:

• Response rate: 44-55% in first-line treatment 4, 5
• Median progression-free survival: 7.7-8.0 months 1, 4
• Median overall survival: 19.5-20 months 4, 5

Toxicity Profile and Management

Common Toxicities:

• Hand-foot syndrome: 31% (any grade), requiring close monitoring and early dose adjustment 1
• Peripheral sensory neuropathy: 85% (any grade), 27% overall neurotoxicity 1, 4
• Diarrhea: grade 3-4 in 10-28% of patients 1, 6, 5
• Myelosuppression is uncommon: grade 3-4 neutropenia only 7-15% 1, 6, 4

Specific Monitoring Requirements:

Monitor capecitabine toxicity closely:

• Patients with diminished creatinine clearance require dose modification 1
• Adjust capecitabine dose at earliest signs of hand-foot syndrome 1
• Interestingly, capecitabine-related hand-foot syndrome correlates with improved overall survival (75.8 vs 41.0 months) 1

Monitor oxaliplatin neurotoxicity at each visit:

• Assess for peripheral neuropathy before each cycle 1
• Discontinue if grade ≥2 neuropathy develops 1
• Do not restart oxaliplatin until near-total resolution of neurotoxicity 1

Treatment Monitoring

Use CT chest/abdomen/pelvis with contrast or chest CT with abdominal/pelvic MRI to monitor treatment response. 1

Critical pitfall: Do not use PET/CT to monitor therapy progress. 1, 3

Subsequent Therapy After Progression

Upon progression on CapeOX, transition to FOLFIRI-based second-line therapy:

• Irinotecan 180 mg/m² IV day 1 2
• Leucovorin 400 mg/m² IV day 1 2
• 5-FU 400 mg/m² IV bolus day 1, then 2,400 mg/m² continuous infusion over 46-48 hours 2
• Every 2 weeks 2
• Consider adding bevacizumab (preferred), ziv-aflibercept, or ramucirumab 1
• For KRAS/NRAS wild-type: consider irinotecan plus cetuximab or panitumumab 1

Special Populations

For patients not appropriate for intensive therapy:

• Consider single-agent capecitabine or infusional 5-FU/leucovorin ± bevacizumab 1
• For dMMR/MSI-H tumors only: nivolumab or pembrolizumab as alternative 1

For irinotecan use in subsequent lines:

• Use caution in patients with Gilbert's disease or elevated bilirubin 1
• Consider UGT1A1 testing, though clinical practice guidelines not established 1