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Clinical Therapy Trials |
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 Medical Center, 220 Sands Building, Research Drive, Durham, NC 27710 USA (john.sampson{at}duke.edu).
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)-
. TGF- 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 anticonvulsants, 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.
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