Combination Targeted Therapy With Sorafenib and Bevacizumab Results in Enhanced Toxicity and Antitumor Activity

摘要: Purpose Sorafenib inhibits Raf kinase and vascular endothelial growth factor (VEGF) receptor. Bevacizumab is a monoclonal antibody targeted against VEGF. We hypothesized that the complementary inhibition of VEGF signaling would have synergistic therapeutic effects. Patients Methods had advanced solid tumors, Eastern Cooperative Oncology Group performance status 0 to 1, good end-organ function. A phase I dose-escalation trial sorafenib bevacizumab was initiated at below-recommended single-agent doses because possible overlapping toxicity: 200 mg orally twice daily intravenously 5 mg/kg (dose level [DL] 1) or 10 (DL2) every 2 weeks. Additional patients were enrolled maximum-tolerated dose (MTD). Results Thirty-nine treated. DL1 MTD administered in cohort (N = 27). Dose-limiting toxicity DL2 grade 3 proteinuria thrombocytopenia. Adverse events included hypertension, hand-foot syndrome, diarrhea, tra...