e13079 Background: High levels of VEGF protein correlate with a poor prognosis translating into poor OS of cancer patients. Bevacizumab in combination with paclitaxel significantly prolongs PFS and increases the objective RR in patients with breast cancer. Serum levels of VEGF increase, in a dose-dependent manner, with all oral TKIs inhibiting VEGFR-2; this reflects a potential escape mechanism of the tumor, consequently overcoming antiangiogenic TKI activity. Combination of sorafenib plus bevacizumab has impressive clinical activity in patients with mRCC, potentially due to overcoming such escape mechanisms. Methods: Titration of the minimal effective (MED) or maximum tolerable dose (MTD) of bevacizumab in combination with regular dosed weekly paclitaxel (90 mg/m2 d1,8,15 q4wks) and continuous oral sorafenib (200 mg bid), that is sufficient to suppress the increase of VEGF levels. A total of 3-6 pts have been or will be treated per dose level with 0 mg, 1 mg, 2 mg, 3 mg and 5 mg bevacizumab q2wks, respectively. Blood levels of VEGF are assessed at baseline, and 8 h post-dose of first sorafenib on days 1 and 15 before the initial dose of bevacizumab, and thereafter before every bevacizumab infusion. Results: Currently 12 pts with various solid tumors were enrolled with bevacizumab doses of 0 mg (n=4), 1 mg (n=6), and 2 mg (n=2). Drug-related adverse events (AEs) observed so far were predominantly hand-foot- syndrome (HFS) (6 pts; CTC 3: 3pts), rash (CTC3: 1pt), stomatitis (3 pts; CTC3: 1 pt), PNP (2 pts; CTC3: 1 pt), diarrhea (CTC 3: 2 pts), granulocytopenia (CTC4: 1 pt), hoarseness (2 pts; CTC3: 1 pt). Treatment-related AEs leading to dose reduction, interruption or discontinuation were HFS (2 pts) and PNP (1 pt). So far, toxicities were not related to the dose of bevacizumab. Currently 9 pts are evaluable for response according to RECIST (ongoing SD: 8 pts, PD: 1 pt). Preliminary VEGF-data support the biological activity of the treatment. Conclusions: The combination of paclitaxel with sorafenib and bevacizumab is potentially highly efficacious, but toxicities might require special precautions. MED or MTD of bevacizumab in this combination have not been reached yet. No significant financial relationships to disclose.