In vivo metabolic activity and transcriptional profiling in melanoma (MM) patients during sorafenib and dacarbazine (DTIC) treatment.

8575 Background: The multi-tyrosine kinase inhibitor sorafenib affects the Raf/Mek/Erk and VEGF pathway. The therapy impact on in vivo metabolic activity and transcriptional profiling was investigated. Methods: Single-arm investigator-initiated pilot study enrolled 13 first-line stage IV MM patients (LDH > 1.1 ULN) with metastases accessible for repeated biopsies. Patients were treated with sorafenib (400 mg bid, day 1-56) and DTIC (1,000 mg/m2, day 14, 42). Primary endpoints were changes in glucose uptake (PERCIST 1.0), S100 and LDH serum levels. Secondary endpoints were determination of differentially expressed genes and alternative splicing events during treatment. PET/CT, serum S100, LDH and biopsies were taken on screening, day 10, 16, and 60. Transcriptional profiling was performed using Human Exon 1.0 WT microarrays (Affymetrix). Differentially expressed genes and alternative splicing events were determined by R-Bioconductor using exonmap, limma, stats and samr packages. Enrichment analysis was per...