title: Complete response of a recurrent, multicentric malignant glioma in a patient treated with phenylbutyrate.
abstract: Sodium phenylbutyrate is a biological-response modifier that acts as a dose-dependent inhibitor of glioma cell proliferation, migration, and invasiveness in vitro, possibly by inhibition of urokinase and c-myc pathways. Despite its biological activity in vitro, there have not been any prior reports of efficacy in the treatment of human malignant gliomas. We report a 44-year-old female with a recurrent, multicentric, malignant glioma who experienced a durable remission lasting more than four years. The patient initially presented with seizures caused by a biopsy-proven anaplastic astrocytoma of the frontal lobe. The patient was treated with radiation therapy and Procarbazine-CCNU-Vincristine (PCV). However, the tumor progressed and extended to the corpus callosum with midline shift, refractory to four cycles of continuous 72-h infusion of BCNU/Cisplatinum. Additional enhancing lesions appeared in the left frontal and left temporal lobes. The patient was started on sodium phenylbutyrate, 18 g daily in three divided oral doses, and reduced to 9 g/day and eventually to 4.5 g/day to eliminate mild, reversible side effects. Four years later, the patient has a KPS functional score of 100%. Phenylbutyrate is a well-tolerated, oral agent that shows potential for the treatment of malignant gliomas. Further studies should be considered to identify a subset of patients that have tumors sensitive to phenylbutyrate, either as a single agent or in combination with radiation therapy or other chemotherapeutic agents.
authors.affiliation: Neuro-Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612-9497, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Baker
authors.forename: Steven
authors.initials: S
authors.lastname: Brem
authors.forename: Stephanie
authors.initials: S
authors.lastname: Daniels
authors.forename: Beverly
authors.initials: B
authors.lastname: Sherman
authors.forename: Surasak
authors.initials: S
authors.lastname: Phuphanich
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008130:Lomustine / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D010654:Phenylbutyrates / Q000627:therapeutic use*; D011344:Procarbazine / Q000627:therapeutic use; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D010654:Phenylbutyrates; D011344:Procarbazine; D014750:Vincristine; D008130:Lomustine; C075773:4-phenylbutyric acid