CONTINUOUS EXPOSURE ORAL PHENYLBUTYRATE 3 TIME DAILY SCHEDULE

University Of Pennsylvania, Philadelphia PA

Investigators

Linked publications & trials

Abstract

Phenylbutyrate, a potential tumor differentiating agent and possible cytotoxic agent, can be given safely to children and adults with urea cycle disorders. Its safety and toxicity are being evaluated in patients with refractory solid tumors using varied schedules and routes of administration. Most clinical trials to date have excluded patients with primary CNS tumors or patients with CNS metastases because of potential side-effects of altering intracranial pressure. This CNS tumor exclusion is despite pre-clinical models suggesting significant anti-tumor activity of phenylbutyrate against malignant glioblastoma, and other solid tumors. Mechanism of action studies continue in the pre-clinical lab. This study is designed to evaluate the safety and toxicity of orally administered phenylbutyrate given three times daily to patients with refractory CNS tumors until evidence of tumor progression. Theoretically, a tumor-differentiating agent requires chronic administration. This schedule examines the tolerability of continued exposure phenylbutyrate. Attempts to excalate the dose of drug will be monitored by pharmacokinectics to achieve desired plasma levels of 2-6 mmol/L. To assist the laboratory with possible mechanisms of action of phenylbutyrate, various bioassays and tissue specimens will be evaluated to determine in vivo bioactivity of the drug. Purpose: 1) To determine maximum tolerated dose of phenylbutyrate taken 3 times a day in patients with relapsed gliomas. 2) To describe the pharmacokinetics of oral phenylbutyrate, attempting to achieve plasma levels of 2-6 mmole/L. 3) To evaluate therapeutic activity and correlate with bioassays.