Progress report of a Phase I study of the intracerebral microinfusion of a recombinant chimeric protein composed of transforming growth factor (TGF)-alpha and a mutated form of the Pseudomonas exotoxin termed PE-38 (TP-38) for the treatment of malignant brain tumors

J Neurooncol. 2003 Oct;65(1):27-35. doi: 10.1023/a:1026290315809.


TP-38 is a recombinant chimeric targeted toxin composed of the EGFR binding ligand TGF-alpha 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / mortality
  • Drug Evaluation, Preclinical
  • Exotoxins / administration & dosage*
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / mortality
  • Humans
  • Infusions, Parenteral
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Pseudomonas aeruginosa / chemistry
  • Recombinant Fusion Proteins / administration & dosage*
  • Survival Rate
  • Transforming Growth Factor alpha / administration & dosage*
  • Treatment Outcome


  • Exotoxins
  • Recombinant Fusion Proteins
  • Transforming Growth Factor alpha