UROLOGICAL ONCOLOGY

High frequency of intracerebral hemorrhage in metastatic renal carcinoma patients with brain metastases treated with tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptor
Pouessel D, Culine S
Department of Medical Oncology, C.R.L.C. Val d’Aurelle, Montpellier, France
Eur Urol. 2008; 53: 376-81

• Objectives: To report the high incidence of intracerebral hemorrhage (ICH) in patients with metastatic renal cell carcinoma (RCC) treated with the tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptor (VEGFR).
• Methods and Results: Between October 2005 and December 2006, 67 patients with metastatic RCC were treated with sorafenib or sunitinib at the Montpellier Cancer Center in compassionate access programs. The medical records of five (7%) patients who died of ICH during therapy were reviewed retrospectively. Four of them had known brain metastases. Previous radiation therapy had been indicated in two patients. Two patients had a history of hypertension. Death from ICH occurred in the first 2 wk following the onset of treatment. Three other patients with brain metastases who received sorafenib or sunitinib during the same period did not experience ICH.
• Conclusions: The frequency of fatal ICH in RCC patients with brain metastases treated with tyrosine kinase inhibitors targeting the VEGFR seems high. Prospective clinical trials will be necessary for assessing the true incidence and predictive factors related to this toxicity.

• Editorial Comment
  Modern treatment of metastatic renal cancer involves tyrosine kinase inhibitors (TKI). This is an early report on possible lethal complications associated with this therapy in patients with brain metastases. Five cases with lethal brain hemorrhage while under TKI are reported and compared to 3 patients with brain metastases who did had not (yet) experienced any complications. No risk factors could be identified so far. Importantly, brain hemorrhage occurred within 2 – 14 days after onset of TKI medication. Urologists involved in the medical therapy of patients with renal cancer and brain metastases should be aware of immediate the risk of such complications and should report them to the community.

Dr. Andreas Bohle
Professor of Urology
HELIOS Agnes Karll Hospital
Bad Schwartau, Germany
E-mail: boehle@urologie-bad-schwartau.de