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
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- Sampson, J.H., Akabani, G., Archer, G.E. et al. J Neurooncol (2003) 65: 27. doi:10.1023/A:1026290315809
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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.