Table 1.
Summary of clinical trials using convection enhanced delivery (CED) of targeted toxin approaches for the treatment of brain tumors
| Receptor target |
Ligand | Toxin | Clinical Stage |
# of patients |
Main findings | Publication |
|---|---|---|---|---|---|---|
| IL-13Rα2 | IL-13 | PE38 | Phase I | 46 | Interim analysis of three Phase I trials. | Kunwar et al., 2003 |
| IL-13Rα2 | IL-13 | PE38 | Phase I | 22 | MTD was established as 0.5 µg/ml administered via CED. | Vogelbaum et al., 2007 |
| IL-13Rα2 | IL-13 | PE38 | Phase I | 51 | Final analysis of three Phase I trials: MTD was established as 0.5 µg/ml administered via CED. Infusion duration of up to 6 days was well tolerated. Postoperative catheter placement is critical for optimal drug distribution. | Kunwar et al., 2007 |
| IL-13Rα2 | IL-13 | PE38 | Phase III | 296 | Efficacy of drugs delivered by CED may be hampered by ineffective delivery. | Sampson et al., 2010 |
| IL-13Rα2 | IL-13 | PE38 | Phase III | 296 | No survival difference between IL13-PE38QQR when compared to Gliadel wafers | Kunwar et al., 2010 |
| IL-4R | IL-4 | PE38 | Phase I | 9 | No systemic toxicity observed. Necrosis was observed in 6 of 9 patients. | Rand et al., 2000 |
| IL-4R | IL-4 | PE38 | Phase I/II | 31 | No drug-related systemic toxicity; treatment-related adverse effects were limited to the central nervous system. MTD was defined as 6 µg/ml × 40ml. | Weber et al., 2003 |
| IL-4R | IL-4 | PE38 | Phase I/II | 31 | Case study of long-term survivor. | Rainov et al., 2005 |
| EGFR | TGFα | PE38 | Phase I | 20 | Progress Report: 3 of 15 patients, with residual disease at the time of therapy, demonstrated radiographic responses and one patient with a complete response that survived longer than 83 weeks | Sampson et al., 2003 |
| EGFR | TGFα | PE38 | Phase I | 20 | Case Study of long-term survivor. | Sampson et al., 2005 |
| EGFR | TGFα | PE-38 | Phase I | 20 | Final Results: MTD was not reached. Dose escalation was stopped at 100 ng/ml due to inconsistent drug delivery. | Sampson et al., 2008 |
| Transferrin-R | Transferrin | DT | Phase I | 18 | No symptomatic systemic toxicity occurred. MTD was defined as 0.67 µg/ml × 40ml. | Laske et al., 1997 |
| Transferrin-R | Transferrin | DT | Phase II | 31 | 35% of the patients displayed complete or partial responses, and only 38% of the patients had progressive disease after treatment. Toxicities associated with Tf-CRM107 were progressive cerebral edema and seizures | Weaver et al., 2003 |