Is it necessary to withhold capecitabine (a chemotherapy agent) during stereotactic radiotherapy to bone metastasis and if so, for how long?

Withholding Capecitabine During Stereotactic Radiotherapy to Bone Metastases

Capecitabine should be withheld during stereotactic body radiotherapy (SBRT) to bone metastases, particularly when treating spinal metastases, due to its potential radiosensitizing effect that may increase toxicity. While specific guidelines on the timing are limited, it is prudent to withhold capecitabine at least 7 days before and after SBRT based on available evidence.

Rationale for Withholding Capecitabine

Radiosensitizing Properties and Toxicity Concerns

• Capecitabine acts as a radiosensitizer, which can increase both the efficacy and toxicity of radiation therapy 1
• When used concurrently with stereotactic radiosurgery for brain metastases, capecitabine has been identified as a risk factor for adverse radiation effects in multivariate analysis 1
• Particular attention is needed when conventional RT or SBRT is performed in conjunction with systemic treatments due to their potential radiosensitizing effects 2

Specific Concerns with Bone Metastases

• SBRT to bone metastases, especially spinal metastases, carries risks including:
  • Vertebral compression fracture (VCF) in 10-20% of cases 2
  • Radiation myelopathy (though rare at <2%) 2
  • Pain flare in up to 30% of patients 2

Recommended Approach

Timing of Capecitabine Withholding

While there are no definitive guidelines specifically addressing capecitabine withholding during SBRT for bone metastases, a prudent approach based on clinical practice would be:

1. Withhold capecitabine at least 7 days before SBRT
2. Resume capecitabine no earlier than 7 days after completion of SBRT
3. Consider longer withholding periods (10-14 days) for high-dose single fraction SBRT

Special Considerations

• Spinal metastases: Exercise extra caution due to risk of spinal cord toxicity
• Single high-dose fractions: Higher risk of toxicity compared to multi-fraction regimens 2
• Large target volumes: Increased risk of adverse effects with larger treatment volumes 1

Alternative Approaches

If systemic therapy cannot be interrupted:

• Consider conventional fractionated radiotherapy instead of SBRT
• Use lower doses of SBRT with more fractions to reduce toxicity risk
• Consider alternative systemic therapies with less radiosensitizing potential during the radiation period

Monitoring and Management

• Monitor closely for radiation toxicity, especially:
  • Pain flare (may require prophylactic dexamethasone) 2
  • Vertebral compression fractures 2
  • Myelopathy symptoms if treating spinal metastases

Conclusion

The radiosensitizing properties of capecitabine make withholding this agent during SBRT to bone metastases advisable to reduce the risk of serious adverse effects. While specific guidelines on timing are limited, a conservative approach of withholding capecitabine for at least 7 days before and after SBRT represents a reasonable clinical practice to minimize toxicity while maintaining overall treatment efficacy.