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Neuro-Oncology 2005 7(1):90-96; doi:10.1215/S1152851703000589
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© 2005 by the Society forNeuro-Oncology

Sustained radiographic and clinical response in patient with bifrontalrecurrent glioblastoma multiforme with intracerebral infusion of therecombinant targeted toxin TP-38: Case study

John H. Sampson2, David A. Reardon, Allan H. Friedman, Henry S. Friedman, R. Edward Coleman, Roger E. McLendon, Ira Pastan and Darell D. Bigner

Duke University Medical Center, Durham, NC 27710(J.H.S., D.A.R., A.H.F., H.S.F., R.E.C., R.E.M., D.D.B.); National Institutes of Health, Bethesda, MD 20892 (I.P.);USA

2 Address correspondence to John H. Sampson, Box 3050, Duke University MedicalCenter, 220 Sands Building, Research Drive, Durham, NC 27710 USA(john.sampson{at}duke.edu).


  Abstract

Glioblastoma multiforme remains refractory to conventional therapy, andnovel therapeutic modalities are desperately needed. TP-38 is a recombinantchimeric protein containing a genetically engineered form of the cytotoxicPseudomonas exotoxin fused to transforming growth factor(TGF)-{alpha}. TGF-{alpha} binds with high affinity to the epidermal growthfactor receptor, which is uniformly overexpressed in malignant gliomas, oftenbecause of gene amplification. Prior to therapy with TP-38, the patientdescribed here was completely refractory to multiple other therapies, withradiographic and pathologic evidence of tumor progression. After therapy, sheimproved clinically, was weaned off steroids and anticonvulsants, andexperienced a progressive decrease in enhancing tumor volume. Despite multipleprior recurrences, she has not progressed for >43 months after TP-38therapy. Small remaining areas of enhancement demonstrate no evidence of tumorhistologically and are hypometabolic on positron emission tomography. Thisreport describes a dramatic and sustained clinical and radiographic responsein a patient with a bifrontal glioblastoma multiforme treated withintratumoral infusion of a novel targeted toxin, TP-38.

Received October 24, 2003; Accepted August 25, 2004


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