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.
OBJECTIVE
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).


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.
Pouessel
Damien
D
Department of Medical Oncology, C.R.L.C. Val d'Aurelle, Montpellier, France.
Culine
Stéphane
S
D000328:Adult; D000368:Aged; D001557:Benzenesulfonates / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D002292:Carcinoma, Renal Cell / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D002543:Cerebral Hemorrhage / Q000209:etiology* / Q000401:mortality; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011725:Pyridines / Q000009:adverse effects*; D011758:Pyrroles / Q000009:adverse effects*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D000077157:Sorafenib; D000077210:Sunitinib