Sustained radiographic and clinical response in patient with bifrontal recurrent glioblastoma multiforme with intracerebral infusion of the recombinant targeted toxin TP-38: case study.
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.
Sampson
John H
JH
Duke University Medical Center, Durham, NC 27710, USA. john.sampson@duke.edu
Reardon
David A
DA
Friedman
Allan H
AH
Friedman
Henry S
HS
Coleman
R Edward
RE
McLendon
Roger E
RE
Pastan
Ira
I
Bigner
Darell D
DD
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
D005098:Exotoxins; D011993:Recombinant Fusion Proteins; D016211:Transforming Growth Factor alpha