What is Xeloda (Capecitabine)?
Xeloda (capecitabine) is an oral fluoropyrimidine chemotherapy agent that functions as a prodrug, converting to 5-fluorouracil (5-FU) preferentially within tumor cells through a three-step enzymatic cascade. 1
Mechanism of Action and Formulation
Capecitabine is designed to be selectively activated at the tumor site, which reduces systemic toxicity compared to intravenous 5-FU. 1, 2 The drug undergoes enzymatic conversion primarily within cancer cells, with the final step catalyzed by thymidine phosphorylase, which is present in higher concentrations in tumor tissue. 2, 3
The medication is available as film-coated tablets in two strengths:
- 150 mg tablets (light peach-colored)
- 500 mg tablets (peach-colored) 1
FDA-Approved Indications
Xeloda is approved for treating:
- Adjuvant treatment of colon cancer after surgery 1
- Metastatic colorectal cancer 1
- Metastatic breast cancer in combination with docetaxel 1
- Metastatic breast cancer as monotherapy after failure of anthracycline and taxane therapy 1
Clinical Use in Cancer Treatment
Colorectal Cancer Applications
In colorectal cancer, capecitabine serves as an interchangeable alternative to intravenous 5-FU/leucovorin in both adjuvant and metastatic settings. 4 The Chinese Society of Clinical Oncology (CSCO) 2024 guidelines list capecitabine as the preferred fluoropyrimidine monotherapy option for adjuvant treatment, administered at 1,250 mg/m² orally twice daily on days 1-14, repeated every 3 weeks for 8 cycles. 4
When combined with oxaliplatin (CAPEOX or XELOX regimen), capecitabine demonstrates equivalent efficacy to FOLFOX and is the preferred combination regimen based on the IDEA study results. 4 The CAPEOX regimen consists of oxaliplatin 130 mg/m² IV on day 1 plus capecitabine 1,000 mg/m² orally twice daily on days 1-14, repeated every 3 weeks. 4
Rectal Cancer Applications
In rectal cancer, capecitabine combined with radiation therapy is an established treatment option, though classified as category 2B by NCCN due to limited phase III data. 4 It can be used in both preoperative and postoperative chemoradiation settings. 4
Gastric and Esophagogastric Cancer
The REAL-2 trial demonstrated that capecitabine is as effective as 5-FU in advanced esophagogastric cancer, with similar toxicity profiles. 4 In the ML 17032 trial, capecitabine plus cisplatin (XP regimen) showed superior overall response rate (41% vs 29%) and overall survival (10.5 vs 9.3 months) compared to 5-FU plus cisplatin. 4
Anal Cancer
Capecitabine serves as an acceptable alternative to infusional 5-FU when combined with mitomycin and radiation for stage I-III anal cancer. 4 Retrospective studies show no significant differences in clinical complete response, locoregional control, or overall survival compared to 5-FU-based regimens, with potentially lower grade 3/4 hematologic toxicities. 4
Administration Guidelines
Capecitabine must be taken within 30 minutes after completing a meal (breakfast and dinner) with water. 1 The drug is administered in two daily doses approximately 12 hours apart. 1
If a dose is missed, patients should not take the missed dose and should not double the next dose. 1
Key Toxicity Profile and Management
Hand-Foot Syndrome (Palmar-Plantar Erythrodysesthesia)
Hand-foot syndrome is the most characteristic adverse effect of capecitabine, affecting up to 73% of patients, with 11% experiencing grade 3 events. 5 This toxicity is significantly more common with capecitabine than with intravenous 5-FU regimens. 4 Interestingly, capecitabine-related hand-foot syndrome has been associated with improved overall survival (75.8 vs 41.0 months). 4
Gastrointestinal Toxicity
Diarrhea incidence increases when capecitabine is combined with other agents. 4, 5 For grade 3-4 diarrhea with neutropenia, fever, or reduced oral intake, immediate hospitalization may be required. 5
Hematologic Effects
Capecitabine demonstrates significantly lower incidence of grade 3/4 myelotoxicity compared to infusional 5-FU-based chemotherapy. 2 However, thrombocytopenia is more common when combined with other agents. 5
Geographic and Population Variations
North American patients experience higher incidence of adverse events with certain capecitabine doses compared to patients from other countries. 4 A gradient of fluoropyrimidine toxicity exists: high in the US and low in East Asia. 2
Patients over 65 years have higher risk of severe toxicity (34% grade 3 or higher), including treatment-related deaths. 5
Critical Drug Interactions and Contraindications
Warfarin Interaction
Capecitabine significantly increases the anticoagulant effect of warfarin (Coumadin), potentially leading to serious bleeding complications. 1 Patients taking warfarin require more frequent INR monitoring and dose adjustments of the anticoagulant. 1
Absolute Contraindications
Do not prescribe capecitabine to patients who:
- Are nursing (drug passes into breast milk) 1
- Have known dihydropyrimidine dehydrogenase (DPD) deficiency (3-5% of population may experience life-threatening toxicity) 5, 1
- Are allergic to capecitabine or 5-fluorouracil 1
Renal Impairment
Patients with diminished creatinine clearance require dose modification since capecitabine elimination is primarily renal. 4, 5, 1
Monitoring Requirements
Close monitoring is essential to enable dose adjustments at the earliest signs of toxicity, particularly hand-foot syndrome. 4 For grade 1 toxicity, treatment should continue with close monitoring. 5