Interstitial docetaxel (taxotere), carmustine and combined interstitial therapy: a novel treatment for experimental malignant glioma.
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.
Sampath
Prakash
P
Department of Clinical Neurosciences Program in Neurosurgery, Brown Medical School, Rhode Island Hospital, Providence, RI 02903, USA. prakash_sampath@hotmail.com
Rhines
Laurence D
LD
DiMeco
Francesco
F
Tyler
Betty M
BM
Park
Michael C
MC
Brem
Henry
H
D020341:Absorbable Implants / Q000009:adverse effects*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000009:adverse effects / Q000493:pharmacokinetics; D000077143:Docetaxel; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D007276:Injections, Intraventricular; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011108:Polymers / Q000008:administration & dosage / Q000009:adverse effects; D051381:Rats; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
D003692:Delayed-Action Preparations; D011108:Polymers; D043823:Taxoids; D000077143:Docetaxel; D002330:Carmustine