APhase I Trial of the Oral, Multikinase Inhibitor Sorafenib in

Abstract Purpose: This study evaluated the safety, maximum tolerated dose, pharmacokinetics, and antitumor activity of sorafenib, a multikinase inhibitor, combined with paclitaxel and carboplatin in patients with solid tumors. Patients and Methods: Thirty-nine patients with advanced cancer (24 with melanoma) received oral sorafenib 100, 200, or 400 mg twice daily on days 2 to 19 of a 21-day cycle. All patients received carboplatin corresponding to AUC6 and 225 mg/m2 paclitaxel on day 1. Pharmacokinetic analyses were done for sorafenib on days 2 and19 of cycle 1and for paclitaxel on day1of cycles1and 2. Pretreatment tumor samples from17melanoma patients were analyzed for BRAF mutations. Results: Sorafenib was well tolerated at the doses evaluated.The most frequent severe adverse events were hematologic toxicities (grade 3 or 4 in 33 patients, 85%). Twenty-seven (69%) patients had sorafenib-related adverse events, the most frequent of which were dermatologic events (26 patients, 67%). Exposure to paclitaxel was not altered by intervening treatment with sorafenib.Treatment with sorafenib, paclitaxel, and carboplatin resulted in one complete response and nine partial responses, all among patients withmelanoma.There was no correlation betwee