Interstitial Chemotherapy of Malignant Brain Tumours

The poor prognosis of patients suffering from primary brain tumours (http://www.moffitt.usf.edu/pubs/ccj/v5n2/toc.html) has not significantly changed despite the development of new surgical and irradiation techniques. Interstitial chemotherapy (http://www.moffitt.usf.edu/pubs/ccj/v5n2/article4.html) is an innovative chemotherapeutic approach. In 1996, in cooperation with Prof. Dr. A. Göpferich (Pharmaceutical Technology) we started to develop biodegradable and programmable implants loaded with various cytostatics either alone or in combination with non-cytotoxic substances such as hyluronidase. Meanwhile, for Gliadel^TM, a BCNU loaded wafer (http://www.gliadel.net/health_professional/default.html), a commercially available preparation approved for local treatment of recurrent glioblastoma multiforme, an increase in 6 months survival has been described. Although efficacy of this therapeutic principle has been demontrated, with respect to median survival of the patients increasing by only 8 weeks (28 weeks for Gliadel^TM Wafer) compared with 20 weeks for placebo wafer the results of the study are still unsatisfactory. Using cytostatic-loaded biodegradable implants we found in nude mice bearing orthotopic human glioblastoma that a 5-fold increase of the cytostatic/polymer ratio for BCNU compared to the commercial composition resulted in long term remissions. As other cytostatics such as paclitaxel showed even more promising effects than the high dose BCNU implants, the optimisation of this therapeutic approach is subject of ongoing research.

Selected publications and abstracts

W. Vogelhuber, T. Spruß, G. Bernhardt, A. Buschauer, A. Göpferich, Efficacy of BCNU and paclitaxel loaded subcutaneous implants in the interstitial chemotherapy of U-87 MG human glioblastoma xenografts, Intern. J. Pharmaceutics 238, 111 - 121 (2002).

W. Vogelhuber, P. Rotunno, A. Gazzaniga, T. Spruss, G. Bernhardt, A. Buschauer, A. Göpferich, Programmable biodegradable implants. J. Contr. Release, 73, 75-88, (2001).

W. Vogelhuber, T. Spruss, G. Bernhardt, A. Buschauer, A. Göpferich, Efficacy of locally administered BCNU and Paclitaxel in a subcutaneous tumor model in nude mice. 3rd World Meeting APV/APGI Berlin, 257-258 (2000).