Phase I study of panobinostat in combination with bevacizumab for recurrent high-grade glioma.

摘要: Bevacizumab is frequently used to treat patients with recurrent high-grade glioma (HGG), but responses are generally not durable. Panobinostat a histone deacetylase inhibitor anti-neoplastic and anti-angiogenic effects may work synergistically VEGF inhibitors. We performed phase I study evaluate the safety tolerability of combination orally administered panobinostat bevacizumab in HGG. Patients HGG were treated on 3 + trial design. received 10 mg/kg every other week oral panobinostat. The starting dose was 20 mg three times per week, weekly (cohort 1). Due concerns for thrombocytopenia dosing regimen, protocol amended examine an regimen. Cohort 2 cohort 30 week. Dose-limiting toxicity during first days determine maximum-tolerated dose. Twelve (median age 50, median KPS 90) enrolled. One dose-limiting (DLT) (Grade thrombocytopenia) observed 1. No DLTs cohorts 3. following grade toxicities seen one patient each: thrombocytopenia, hypophosphatemia, esophageal hemorrhage, deep venous thrombosis. There no 4 or 5 toxicities. partial seven stable disease. recommended doses further A II clinical underway.