A pediatric phase 1 trial of vorinostat and temozolomide in relapsed or refractory primary brain or spinal cord tumors: a Children's Oncology Group phase 1 consortium study.

ABSTRACT:

Purpose

We conducted a pediatric phase I study to estimate the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetic properties of vorinostat, a histone deacetylase (HDAC) inhibitor, when given in combination with temozolomide in children with refractory or recurrent CNS malignancies.

Patients and methods

Vorinostat, followed by temozolomide approximately 1 hour later, was orally administered, once daily, for 5 consecutive days every 28 days at three dose levels using the rolling six design. Studies of histone accumulation in peripheral blood mononuclear cells were performed on Day 1 at 0, 6, and 24 hours after vorinostat dosing. Vorinostat pharmacokinetics (PK) and serum MGMT promoter status were also assessed.

Results

Nineteen eligible pa

SUBMITTER: Hummel TR 

PROVIDER: S-EPMC4139006 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature