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.
Published
Journal Article
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.
Full Text
Duke Authors
- Archer, Gerald Edward
- Bigner, Darell Doty
- Friedman, Allan Howard
- Friedman, Henry Seth
- Herndon II, James Emmett
- McLendon, Roger Edwin
- Provenzale, James Michael
- Sampson, John Howard
- Wong, Terence Z.
- Yuan, Fan
- Zalutsky, Michael Rod
Cited Authors
- Sampson, JH; Akabani, G; Archer, GE; Bigner, DD; Berger, MS; Friedman, AH; Friedman, HS; Herndon, JE; Kunwar, S; Marcus, S; McLendon, RE; Paolino, A; Penne, K; Provenzale, J; Quinn, J; Reardon, DA; Rich, J; Stenzel, T; Tourt-Uhlig, S; Wikstrand, C; Wong, T; Williams, R; Yuan, F; Zalutsky, MR; Pastan, I
Published Date
- October 1, 2003
Published In
Volume / Issue
- 65 / 1
Start / End Page
- 27 - 35
PubMed ID
- 14649883
Pubmed Central ID
- 14649883
Electronic International Standard Serial Number (EISSN)
- 1573-7373
International Standard Serial Number (ISSN)
- 0167-594X
Digital Object Identifier (DOI)
- 10.1023/a:1026290315809
Language
- eng