When is Capecitabine (Xeloda) used in the treatment of Invasive Ductal Carcinoma (IDC)?

Capecitabine Use in Invasive Ductal Carcinoma (IDC)

Capecitabine should be offered to patients with early-stage, HER2-negative IDC who have residual invasive disease after completing standard preoperative anthracycline- and taxane-based chemotherapy, with preferential use in triple-negative breast cancer. 1

Primary Indication: Post-Neoadjuvant Residual Disease

Adjuvant capecitabine is specifically indicated for patients with HER2-negative IDC who have pathologic residual invasive disease at surgery following standard preoperative chemotherapy. 1

Treatment Protocol

• Dosing: 1,250 mg/m² orally twice daily on days 1-14 of a 21-day cycle 1
• Duration: 6-8 cycles 1
• Timing: Initiated after completion of surgery in patients who received neoadjuvant anthracycline and/or taxane-based therapy 1

Survival Benefits

• Disease-free survival: 74.1% vs 67.6% at 5 years (HR 0.70; 95% CI 0.53-0.92; absolute benefit 6.5%) 1, 2
• Overall survival: 89.2% vs 83.6% (HR 0.59; 95% CI 0.39-0.90; absolute benefit 5.6%) 1, 2

Preferential Patient Populations

Triple-Negative Breast Cancer (Strongest Indication)

The expert panel preferentially supports capecitabine use in hormone receptor-negative, HER2-negative (triple-negative) breast cancer due to superior outcomes. 1

• Disease-free survival: 69.8% vs 56.1% (HR 0.58; 95% CI 0.39-0.87) 1, 2
• Overall survival: 78.8% vs 70.3% (HR 0.52; 95% CI 0.30-0.90) 1, 2
• Long-term follow-up: At 10.3 years median follow-up, triple-negative patients maintained improved recurrence-free survival and OS 1

Hormone Receptor-Positive Disease

Patients with hormone receptor-positive, HER2-negative IDC also derive benefit, though numerically smaller: 1, 2

• Disease-free survival: 76.4% vs 73.5% (HR 0.81; 95% CI 0.55-1.17) 1, 2
• Overall survival: 93.4% vs 90% (HR 0.73; 95% CI 0.38-1.40) 1, 2

Alternative Setting: Metastatic Disease

In metastatic IDC, capecitabine is a preferred single-agent option, particularly after prior anthracycline and taxane exposure. 1

Metastatic Disease Efficacy

• Overall response rate: 28-30% 1
• Median time to progression: 4.1-4.9 months 1
• Median overall survival: 15.2-19.6 months 1
• Capecitabine demonstrated superior response rates compared to CMF (30% vs 16%) in first-line metastatic treatment 1

Critical Age-Related Dosing Considerations

The standard CREATE-X dose of 1,250 mg/m² twice daily is associated with significantly higher toxicity in patients ≥65 years old. 1

• Patients over 65 have 34% risk of grade 3 or higher toxicity, including treatment-related deaths 3
• Consider starting dose of 1,000 mg/m² twice daily in elderly patients 3
• Close monitoring during the first treatment cycle is essential for all patients 3

Sequencing Considerations with Olaparib

For patients with germline BRCA1/2 mutations and triple-negative IDC with residual disease after preoperative chemotherapy, both capecitabine and olaparib are options. 1

Important caveat: Patients in the OlympiA trial did not receive capecitabine; thus, no data exist on sequencing or to guide selection of one agent over the other. 1

Common Pitfalls to Avoid

• Do not use capecitabine in HER2-positive disease - the CREATE-X trial specifically excluded HER2-positive patients 1
• Do not assume European dosing is appropriate for North American patients - toxicity profiles differ significantly 3
• Do not use in patients without residual disease after neoadjuvant therapy - the indication is specifically for those with pathologic residual invasive disease 1
• Monitor hand-foot syndrome closely - occurs in up to 73% of patients, with 11% experiencing grade 3 events 3
• Screen for DPD deficiency - 3-5% of population may experience potentially life-threatening toxicity 3