Docetaxel (Taxotere) is a hemisynthetic, anti-cancer compound with good preclinical and clinical activity in a variety of systemic neoplasms. We tested its activity against malignant gliomas using local delivery methods. Antitumor activity was assessed in vitro against human (U87 and U80 glioma) and rat brain-tumor (9L gliosarcoma and F98 glioma) cell lines. For in vivo evaluation, we incorporated docetaxel into a biodegradable polymer matrix, determined associated toxicity in the rat brain, and measured efficacy at extending survival in a rat model of malignant glioma. Also, we examined the combined local delivery of docetaxel with carmustine (BCNU) against the experimental intracranial glioma. Rats bearing intracranial 9L gliosarcomas were treated 5 days after tumor implantation with various polymers (placebo, 5% docetaxel, 3.8% BCNU, or 5% docetaxel and 3.8% BCNU combination). Animals receiving docetaxel polymers (n=15, median survival 39.1 days) had significantly improved survival over control animals (n=12, median survival 22.5 days, P=0.01). Similarly, animals receiving BCNU polymers (n=15, median survival 39.3 days, 13.3% long-term survivors) demonstrated an increase in survival compared to the controls (P=0.04). Animals receiving the combination polymers demonstrated a modest increase in survival compared to either chemotherapeutic agent alone (n=14, median survival 54.9 days, 28.6% long-term survivors) with markedly improved survival over controls (P=0.003). We conclude that locally delivered docetaxel shows promise as a novel anti-glioma therapy and that the combination of drug regimens via biodegradable polymers may be a great therapeutic benefit to patients with malignant glioma.
Interstitial docetaxel (Taxotere), carmustine and combined interstitial therapy: a novel treatment for experimental malignant glioma / P. Sampath, L.D. Rhines, F. Dimeco, B.M. Tyler, M.C. Park, H. Brem. - In: JOURNAL OF NEURO-ONCOLOGY. - ISSN 0167-594X. - 80:1(2006 Oct), pp. 9-17.
|Titolo:||Interstitial docetaxel (Taxotere), carmustine and combined interstitial therapy: a novel treatment for experimental malignant glioma|
|Parole Chiave:||biodegradable polymers; carmustine (BCNU); combined interstitial chemotherapy; docetaxel (Taxotere); malignant glioma|
|Settore Scientifico Disciplinare:||Settore MED/27 - Neurochirurgia|
|Data di pubblicazione:||ott-2006|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1007/s11060-006-9159-4|
|Appare nelle tipologie:||01 - Articolo su periodico|
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