title: Sustained radiographic and clinical response in patient with bifrontal recurrent glioblastoma multiforme with intracerebral infusion of the recombinant targeted toxin TP-38: case study.
abstract: Glioblastoma multiforme remains refractory to conventional therapy, and novel therapeutic modalities are desperately needed. TP-38 is a recombinant chimeric protein containing a genetically engineered form of the cytotoxic Pseudomonas exotoxin fused to transforming growth factor (TGF)-alpha. TGF-alpha binds with high affinity to the epidermal growth factor receptor, which is uniformly overexpressed in malignant gliomas, often because of gene amplification. Prior to therapy with TP-38, the patient described here was completely refractory to multiple other therapies, with radiographic and pathologic evidence of tumor progression. After therapy, she improved clinically, was weaned off steroids and anti-convulsants, and experienced a progressive decrease in enhancing tumor volume. Despite multiple prior recurrences, she has not progressed for >43 months after TP-38 therapy. Small remaining areas of enhancement demonstrate no evidence of tumor histologically and are hypometabolic on positron emission tomography. This report describes a dramatic and sustained clinical and radiographic response in a patient with a bifrontal glioblastoma multiforme treated with intratumoral infusion of a novel targeted toxin, TP-38.
authors.affiliation: Duke University Medical Center, Durham, NC 27710, USA. john.sampson@duke.edu
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.forename: Allan H
authors.initials: AH
authors.lastname: Friedman
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
authors.forename: R Edward
authors.initials: RE
authors.lastname: Coleman
authors.forename: Roger E
authors.initials: RE
authors.lastname: McLendon
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
authors.forename: Darell D
authors.initials: DD
authors.lastname: Bigner
mesh_terms: D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005098:Exotoxins / Q000008:administration & dosage*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007276:Injections, Intraventricular; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D011550:Pseudomonas aeruginosa; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D016211:Transforming Growth Factor alpha / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D005098:Exotoxins; D011993:Recombinant Fusion Proteins; D016211:Transforming Growth Factor alpha