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, Sandeep Kunwar, Steve Marcus, Roger E. McLendon, Alison Paolino, Kara Penne, James Provenzale, Jennifer Quinn, David A. Reardon, Jeremy Rich, Timothy Stenzel, S. Tourt-Uhlig, Carol WikstrandTerence Wong, Roger Williams, Fan Yuan, Michael R. Zalutsky, Ira Pastan

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209 Scopus citations

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 25 ng/mL to 100 with a 40 mL infusion volume delivered by two catheters. One patient developed Grade IV fatigue at the 100 ng/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.

Original languageEnglish
Pages (from-to)27-35
Number of pages9
JournalJournal of Neuro-Oncology
Volume65
Issue number1
DOIs
StatePublished - Oct 2003
Externally publishedYes

Keywords

  • Brain neoplasms
  • Convection-enhanced delivery
  • Immunotoxin

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