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Progress Report of a Phase I Study of the Intracerebral Microinfusion of a Recombinant Chimeric Protein Composed of Transforming Growth Factor (TGF)-α and a Mutated form of the Pseudomonas Exotoxin Termed PE-38 (TP-38) for the Treatment of Malignant Brain Tumors

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Abstract

TP-38 is a recombinant chimeric targeted toxin composed of the EGFR binding ligand TGF-α and a genetically engineered form of the Pseudomonas exotoxin, PE-38. After in vitro and in vivo animal studies that showed specific activity and defined the maximum tolerated dose (MTD), we investigated this agent in a Phase I trial. The primary objective of this study was to define the MTD and dose limiting toxicity of TP-38 delivered by convection-enhanced delivery in patients with recurrent malignant brain tumors. Twenty patients were enrolled in the study and doses were escalated from 25ng/mL to 100 with a 40mL infusion volume delivered by two catheters. One patient developed Grade IV fatigue at the 100ng/mL dose, but the MTD has not been established. The overall median survival after TP-38 for all patients was 23 weeks whereas for those without radiographic evidence of residual disease at the time of therapy, the median survival was 31.9 weeks. Overall, 3 of 15 patients, with residual disease at the time of therapy, have demonstrated radiographic responses and one patient with a complete response and has survived greater than 83 weeks.

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Authors and Affiliations

  1. Duke University Medical Center, Durham, NC, USA

    John H. Sampson, Gamal Akabani, Gary E. Archer, Darell D. Bigner, Allan H. Friedman, Henry S. Friedman, James E. Herndon II, Steve Marcus, Roger E. McLendon, Alison Paolino, Kara Penne, James Provenzale, Jennifer Quinn, David A. Reardon, Jeremy Rich, Timothy Stenzel, Sandra Tourt-Uhlig, Carol Wikstrand, Terence Wong, Fan Yuan & Michael R. Zalutsky

  2. UCSF, San Francisco, CA, USA

    Mitchel S. Berger & Sandeep Kunwar

  3. IVAX, Miami, FL, USA

    Roger Williams

  4. NCI, Bethesda, MD, USA

    Ira Pastan

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  1. John H. Sampson
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  2. Gamal Akabani
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  15. Jennifer Quinn
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  22. Roger Williams
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  23. Fan Yuan
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  24. Michael R. Zalutsky
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  25. Ira Pastan
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Sampson, J.H., Akabani, G., Archer, G.E. et al. Progress Report of a Phase I Study of the Intracerebral Microinfusion of a Recombinant Chimeric Protein Composed of Transforming Growth Factor (TGF)-α and a Mutated form of the Pseudomonas Exotoxin Termed PE-38 (TP-38) for the Treatment of Malignant Brain Tumors. J Neurooncol 65, 27–35 (2003). https://doi.org/10.1023/A:1026290315809

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