Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: a dose escalation and pharmacologic study

Neuro Oncol. 2005 Apr;7(2):177-82. doi: 10.1215/S1152851704000183.


We determined the maximum tolerated dose (MTD), toxicity profile, pharmacokinetic parameters, and preliminary efficacy data of oral sodium phenylbutyrate (PB) in patients with recurrent malignant gliomas. Twenty-three patients with supratentorial recurrent malignant gliomas were enrolled on this dose escalation trial. Four dose levels of PB were studied: 9, 18, 27, and 36 g/day. Data were collected to assess toxicity, response, survival, and pharmacokinetics. All PB doses of 9, 18, and 27 g/day were well tolerated. At 36 g/day, two of four patients developed dose-limiting grade 3 fatigue and somnolence. At the MTD of 27 g/day, one of seven patients developed reversible grade 3 somnolence. Median survival from time of study entry was 5.4 months. One patient had a complete response for five years, and no partial responses were noted, which yielded an overall response rate of 5%. Plasma concentrations of 706, 818, 1225, and 1605 muM were achieved with doses of 9, 18, 27, and 36 g/day, respectively. The mean value for PB clearance in this patient population was 22 liters/h, which is significantly higher than the 16 liters/h reported in patients with other malignancies who were not receiving P450 enzyme-inducing anticonvulsant drugs (P = 0.038). This study defines the MTD and recommended phase 2 dose of PB at 27 g/day for heavily pretreated patients with recurrent gliomas. The pharmacology of PB appears to be affected by concomitant administration of P450-inducing anticonvulsants.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Anticonvulsants / therapeutic use
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacology*
  • Area Under Curve
  • Cytochrome P-450 Enzyme System / drug effects
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Female
  • Glioma / drug therapy*
  • Glioma / mortality
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality
  • Phenylbutyrates / adverse effects
  • Phenylbutyrates / blood
  • Phenylbutyrates / pharmacology*
  • Supratentorial Neoplasms / drug therapy*
  • Supratentorial Neoplasms / mortality


  • Anticonvulsants
  • Antineoplastic Agents
  • Phenylbutyrates
  • Cytochrome P-450 Enzyme System