Objective:

To report a case of recurrent intracranial hemorrhage following VEGFR TKI rechallenge in a patient with metastatic renal cell carcinoma without brain metastasis.

Key Findings:

• The patient developed multifocal cerebellar hemorrhages after sunitinib therapy, confirmed by imaging and histopathology to be non-malignant.
• Rechallenge with pazopanib led to recurrent hemorrhage within 4 weeks, resulting in rapid clinical deterioration and death.
• This case underscores the potential risks associated with VEGFR TKI therapy in patients with a history of CNS hemorrhage.

Interpretation:

The findings highlight the need for careful consideration of the risks versus benefits when rechallenging with VEGFR TKIs in patients with prior intracranial hemorrhage. The rapid recurrence of hemorrhage following pazopanib suggests a possible association between VEGFR TKI therapy and increased risk of bleeding in this patient population.

Limitations:

• The findings are based on a single case report, limiting generalizability.
• The timing and safety of VEGFR TKI rechallenge after CNS hemorrhage remain unclear.

Conclusion:

This case illustrates the potential for recurrent intracranial hemorrhage following VEGFR TKI rechallenge in patients with a history of hemorrhagic events. Further studies are needed to establish guidelines for the management of such patients and to better understand the underlying mechanisms involved.