Artikel
Convection-enhanced delivery of paclitaxel (Taxol®) in patients with recurrent glioblastoma multiforme: a phase I/II study
Konvektionsbasierte Gabe von Paclitaxel (Taxol®) bei Patienten mit Glioblastom-Rezidiven: eine Phase I/II-Studie
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Autoren
Veröffentlicht: | 4. Mai 2005 |
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Gliederung
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Objective
Critical issues in chemotherapy of malignant gliomas are systemic toxicity and the ability of bypassing the blood brain barrier. To overcome these problems, direct drug delivery into the brain parenchyma is increasingly used. Effective dose, efficacy and safety of convection-enhanced delivery (CED) of paclitaxel (Taxol®) in patients with recurrent glioblastoma multiforme (GBM) is evaluated in a phase I/II trial.
Methods
8 patients with recurrent GBM were enrolled in this study each completing up to 2 cycles of intratumoural paclitaxel infusion. 1-2 catheters were placed stereotactically into the solid tumour based on MRI and FET-PET data. Paclitaxel dissolved in cremophore® at a concentration of 0.25 - 0.5 mg/ml was infused in a rate of 0.3 ml/h for 5 days resulting in a total dose of 9 - 18 mg paclitaxel. Convection was monitored by MRI including DWI and DTI. Follow-up including MRI and FET-PET was performed at day 28, then bimonthly for 1 year.
Results
Tumours were located within or next to speech or central areas in 7/8 patients. Initial MRI studies demonstrated induction of intratumoural necrosis in 7/8 patients independent of the dose. Partial response (as shown by MRI and PET) was seen in 7/8 patients, stable disease in 1/8. Median progression free survival was 7.0 months, median overall survival was 10.0 months (range 4-15 months). In patients receiving 0.5 mg/ml paclitaxel a permanent neurological deficit was seen in 2/4 patients, temporary deficits during paclitaxel infusion in 1/4 patients. In patients receiving 0.25 mg/ml, no permanent deficits occurred despite partial response in all cases. There were no signs of any systemic toxicity.
Conclusions
According to these preliminary results, CED of paclitaxel at a dose of 0.25 mg/ml is a very effective therapy for patients with recurrent glioblastoma multiforme with a favourable safety profile. Long-term observations with a larger number of patients will follow.