Journal of Neuro-Oncology

, Volume 65, Issue 1, pp 27–35

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

  • John H. Sampson
  • Gamal Akabani
  • Gary E. Archer
  • Darell D. Bigner
  • Mitchel S. Berger
  • Allan H. Friedman
  • Henry S. Friedman
  • James E. Herndon II
  • Sandeep Kunwar
  • 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
  • Roger Williams
  • Fan Yuan
  • Michael R. Zalutsky
  • Ira Pastan
Article

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.

brain neoplasms convection-enhanced delivery immunotoxin 

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Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • John H. Sampson
    • 1
  • Gamal Akabani
    • 1
  • Gary E. Archer
    • 1
  • Darell D. Bigner
    • 1
  • Mitchel S. Berger
    • 2
  • Allan H. Friedman
    • 1
  • Henry S. Friedman
    • 1
  • James E. Herndon II
    • 1
  • Sandeep Kunwar
    • 2
  • Steve Marcus
    • 1
  • Roger E. McLendon
    • 1
  • Alison Paolino
    • 1
  • Kara Penne
    • 1
  • James Provenzale
    • 1
  • Jennifer Quinn
    • 1
  • David A. Reardon
    • 1
  • Jeremy Rich
    • 1
  • Timothy Stenzel
    • 1
  • Sandra Tourt-Uhlig
    • 1
  • Carol Wikstrand
    • 1
  • Terence Wong
    • 1
  • Roger Williams
    • 3
  • Fan Yuan
    • 1
  • Michael R. Zalutsky
    • 1
  • Ira Pastan
    • 4
  1. 1.Duke University Medical CenterDurhamUSA
  2. 2.UCSFSan FranciscoUSA
  3. 3.IVAXMiamiUSA
  4. 4.NCIBethesdaUSA

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