Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: a dose escalation and pharmacologic study.
Neuro Oncol
; 7(2): 177-82, 2005 Apr.
Article
en En
| MEDLINE
| ID: mdl-15831235
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fenilbutiratos
/
Neoplasias Supratentoriales
/
Glioma
/
Recurrencia Local de Neoplasia
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Neuro Oncol
Asunto de la revista:
NEOPLASIAS
/
NEUROLOGIA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido