Publications [#98474] of John H Sampson

Papers Published

1. JH Sampson, G Akabani, GE Archer, DD Bigner, MS Berger, AH Friedman, HS Friedman, JE Herndon, S Kunwar, S Marcus, RE McLendon, A Paolino, K Penne, J Provenzale, J Quinn, DA Reardon, J Rich, T Stenzel, S Tourt-Uhlig, C Wikstrand, T Wong, R Williams, F Yuan, MR Zalutsky, I Pastan, 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., Journal of neuro-oncology, Netherlands, vol. 65 no. 1 (October, 2003), pp. 27-35, ISSN 0167-594X
   (last updated on 2006/06/06)

   Abstract:
   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.

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