Artikel
Safety of combined intra- and peritumoral immune toxin treatment with TGF-alpha in 12 recurrent glioblastomas
Erfahrungen der kombinierten intra- und peritumoralen Immuntoxin-Therapie mit TGF-alpha bei 12 Glioblastomrezidiven
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Autoren
Veröffentlicht: | 23. April 2004 |
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Gliederung
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Objective
Adjuvant treatment of recurrent high-grade glioma with intralesional immune toxin was established for receptor based selective treatment. In previous studies with IL-4 immune toxin, catheter placement was restricted to the recurrent tumour mass and 40 ml agent were administered by convection-enhanced delivery only into the tumour. Due to the low specificity of the ligand and low density of the receptor, toxin doses had to be high (6-15 mg/ml) and led to considerable side effects. The outcome in most of the patients was complicated.
Methods
A new immune toxin with the ligand TGF-alpha (targeting to the EGFR) coupled to pseudomonas exotoxin A is under investigation in patients with recurrent glioblastoma. After needle biopsy three catheters are placed into the tumour and additionally deep into the adjacent infiltration zone within the white matter. Over 67 hours three micro infusion pumps administer a total volume of 40 ml agent. Due to the high density of EGFR in glioma cells and the specific ligand, the toxin doses are 100 times lower (50-100 ng/ml) than previously.
Results
Twelve patients have been recruited so far and the treatment was excellently tolerated in all. There were no side effects except for self-limiting mild headaches in 6 patients and mild reversible deterioration of pre-existing deficits. Despite the administration of 40 ml immune toxin deep into the peritumoral “healthy” white matter, no permanent neurological deterioration, brain oedema or seizures were observed. All patients left the clinic the day after the end of the infusion. In contrast to the intratumoral “high-dose” treatment with IL-4 toxin, we did not observe intratumoral necrosis within the first days after the treatment. Further follow-up will show whether the combined intra- and peritumoral “low-dose” treatment with TGF-alpha will lead to destruction of the macroscopically visible tumour mass and the microscopically scattered tumour cells of the infiltration zone.
Conclusions
Convection enhanced delivery of the TGF-alpha immune toxin in recurrent glioblastoma appears to be safe. Further follow-up will answer the question of the efficacy of this experimental treatment.