Phase I trial of BAY 43-9006 (sorafenib) combined with dacarbazine (DTIC) in metastatic melanoma patients

7508 Background: BAY 43–9006 (BAY) prevents tumor cell proliferation and angiogenesis via blockade of the RAF/MEK/ERK pathway at the level of RAF (RAF-1, wild-type B-RAF, V599E B-RAF) kinase and inhibition of the receptor tyrosine kinases VEGFR-2 and PDGFR-β. In phase I/II trials, BAY was generally well tolerated as a single agent or with concomitant chemotherapy. Methods: This single-centre, open-label, phase I, dose-escalation study was performed to determine the safety profile and maximum tolerated dose (MTD) of BAY administered at 200 (cohort 1) or 400 (cohort 2) mg bid in combination with repeated 21-day cycles of DTIC 1000 mg/m2. In an extension phase (cohort 3), patients (pts) received the MTD of BAY plus DTIC 1000 mg/m2. Results: Pts with metastatic melanoma were enrolled (ECOG PS 0–1) into cohorts 1 (n=3) 2 (n=6) and 3 (n=3). 1 pt died due to PD. The most common drug-related AEs were dermatologic (rash, flushing, hand-foot skin reaction [HFS]); gastrointestinal (nausea, diarrhoea, constipation, v...