BM-30 * INTRA CEREBROPSINAL FLUID CONCENTRATIONS OF VEMURAFENIB IN MELANOMA

Abstract

The prognostic of BRAF mutated melanoma has been improved by Vemurafenib. Nevertheless, the cerebral and extracerebral responses to Vemurafenib may differ. Melanoma are one the most frequent causes of central nervous system metastases among solid tumors in adults. Our aim was to compare the serum and cerebrospinal fluid (CSF) concentrations of Vemurafenib in BRAF mutated melanoma patients presenting with brain metastases (BM) and a suspicion of leptomeningeal metastases (LM). A total of 6 patients were enrolled between February 2012 and March 2013. All patients had provided their written consent. The BRAF mutations were V600E in 5 patients and V600K in one patient. All patients had BM (>3 in 5 patients). Malignant cells were observed in the CSF in only one patient. Serum and CSF samples were performed at the same time while patients received Vemurafenib 960 mg twice a day. The concentrations were determined using liquid chromatography. Serum concentrations varied from 28.9 to 96.1 mg/L and CSF concentrations from 0.12 to 1 mg/L. The mean CSF serum ratio of Vemurafenib concentrations was 0.98% (range, 0.28–2.5%). No clear correlation was observed between the serum and CSF values. The higher concentrations of Vemurafenib in the CSF were observed in the 2 patients previously treated with stereotactic surgery. The great variability observed between patients may be explained by different level of expression and activity of efflux proteins (P-gp, BCRP), but also by the CNS metastases and their treatments.