Phase I and Pharmacokinetic Trial of Phenylbutyrate Given as a Continuous Infusion in Pediatric Patients With Refractory Malignancy
Phenylbutyrate is an aromatic fatty acid that is converted to phenylacetate in vivo by
mitochondrial beta-oxidation to phenylacetate. Preclinical studies have shown that
continuous exposure to phenylacetate or phenylbutyrate can induce tumor cytostasis and
differentiation in a wide variety of cell lines including malignant gliomas and
neuroblastomas. However, phenylbutyrate has been shown to be a more potent differentiating
agent than phenylacetate in a variety of tumor cell lines. In addition, phenylbutyrate
appears to have molecular activities that are distinct from phenylacetate. The objective of
this trial is to determine the maximum tolerated dose and the toxicities of phenylbutyrate
administered as a continuous intravenous infusion for 28 days. In addition, the
pharmacokinetics of phenylbutyrate and its metabolite, phenylacetate, will be studied using
both model-dependent and model-independent parameters.
Interventional
Endpoint Classification: Safety Study, Primary Purpose: Treatment
United States: Federal Government
970051
NCT00001565
December 1996
October 2000
Name | Location |
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National Cancer Institute (NCI) | Bethesda, Maryland 20892 |