gms | German Medical Science

TP-38 is a recombinant chimeric protein composed of the epidermal growth factor receptor (EGFR) binding ligand (TGF-α) and a genetically engineered form of the Pseudomonas exotoxin PE-38. We report preliminary results of a randomized phase II study conducted at multiple European centers. Either of two dose levels of TP-38 (50 ng/ml or 100 ng/ml) was administered to patients with recurrent gliolblastoma in a single treatment consisting of a continuous intratumoural infusion.

This was a non-resection study; patients did not undergo tumour resection immediately prior to treatment. Three catheters were stereotactically placed in investigator-determined locations within the enhancing tumour area. The infusion rate was 0.2 ml/min per catheter. Each catheter delivered 13.4 ml over 67 h. The total volume infused was approximately 40 ml, and the total dose of TP-38 infused was approximately 2μg or 4μg. Patients were followed until death. Tumour response was assessed by MRI every 8 weeks, beginning 4 weeks after treatment. Safety was closely evaluated. Time to progression, progression-free survival, and overall survival were the measured end points.

Thirty-four of the planned 38 patients have been treated thus far. Safety and tolerability have been excellent. The 4-week and 12-week post-infusion MRI scans often showed treatment-related changes that make response assessment difficult. These changes usually resolved by the 20-week post treatment MRI. Preliminary data show that one patient has a complete response 48 weeks after infusion, and another patient showed a partial response over 60 weeks, 24 patients remained stable.

These results in a not highly selected group of patients suffering from recurrent glioblastoma are so promising that we proceed with a second trial where the tumour gets first resected and the area adjacent to the tumour will then be treated by CED of TP38.