A phase I trial of vorinostat and bortezomib in children with refractory or recurrent solid tumors: A Children's Oncology Group study

9522 Background: Vorinostat and bortezomib have demonstrated single agent anti-tumor activity in preclinical models of pediatric solid and CNS tumors, including synergistic anti-tumor activity when the agents are utilized in combination. A pediatric phase I trial was performed to determine the maximal tolerated dose, dose-limiting toxicities (DLTs), and pharmacokinetics (PK) of vorinostat and bortezomib, as well as to assess the impact of bortezomib on NF-κB binding activity and Grp78 protein expression in peripheral blood mononuclear cells (PBMCs). Methods: Oral vorinostat was administered on days 1-5 and 8-12 of a 21 day cycle (starting dose 180 mg/m2/day with dose escalations to 230 and 300 mg/m2/day). Bortezomib (1.3 mg/m2 i.v.) was administered on days 1, 4, 8, and 11. PK and correlative biology studies were performed during cycle 1. Results: 23 eligible patients, 18 male, median age 12 yrs (range, 1-20) were enrolled. 6/23 patients were not fully evaluable for toxicity; 2 did not complete cycle 1, 2...