Incidence of Vasospasm with Xeloda (Capecitabine)
The incidence of coronary vasospasm with capecitabine (Xeloda) is reported to be up to 10%, though the exact rate varies considerably depending on dose, scheduling, and route of administration. 1
Reported Incidence Rates
Fluoropyrimidines as a class (including capecitabine and 5-fluorouracil) cause myocardial ischemia in up to 10% of patients, with the incidence varying based on dosing regimen and administration route 1
Manifest myocardial ischemia occurs in up to 18% of patients treated with fluoropyrimidines 1
Silent myocardial ischemia has been documented in 6-7% of patients on fluoropyrimidine therapy when evaluated with stress testing, suggesting the clinical problem may be underestimated 1
In a retrospective case-control study of 177 patients receiving fluoropyrimidines, 4.5% experienced adjudicated cardiovascular toxicity, though this represents all cardiotoxic events, not exclusively vasospasm 2
Mechanism and Clinical Presentation
The pathophysiology of capecitabine-induced coronary vasospasm is multifactorial and includes: 1
- Direct coronary vasospasm
- Endothelial injury
Chest pain and ischemic ECG changes typically occur at rest rather than during exercise, usually within days of drug administration and sometimes persist even after treatment cessation 1. Most cardiotoxic cases present with chest pain, though a minority present with nonischemic cardiomyopathy 2.
Risk Factors
Patients at higher risk for capecitabine-induced vasospasm include those with: 2
- Pre-existing coronary artery disease (38% prevalence among cases versus 7% in controls, p<0.05)
- Traditional cardiovascular risk factors (trend toward increased prevalence in cases)
Important Clinical Considerations
Capecitabine-induced vasospasm can occur in patients with minimal cardiac risk factors, as demonstrated in case reports of patients developing dramatic ECG changes at rest that resolved with nitrate infusion 3. The first reported case of capecitabine-associated coronary vasospasm occurred in a 70-year-old man with no known coronary disease or major risk factors 4.
The timing is typically early in treatment, with most cases occurring within 48 hours of starting therapy and often during the first cycle 5.
Treatment Implications
Calcium channel blockers and nitrates are the mainstay treatment for coronary vasospasm 1. When vasospasm occurs with capecitabine, the drug should be discontinued immediately 3, 5.
For patients requiring continued fluoropyrimidine therapy after experiencing vasospasm with capecitabine or infusional 5-FU, switching to bolus 5-FU in combination with oxaliplatin (FLOX regimen) is safe and well-tolerated, with no cardiovascular adverse events reported in a series of 10 patients who had previously experienced coronary vasospasm 5.