Interstitial docetaxel (Taxotere), ccarmustine and ccombined interstitial ttherapy: A novel treatment for experimental malignant glioma

Prakash Sampath, Laurence D. Rhines, Francesco DiMeco, Betty M. Tyler, Michael C. Park, Henry Brem

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)9-17
Number of pages9
JournalJournal of Neuro-Oncology
Volume80
Issue number1
DOIs
Publication statusPublished - Oct 2006

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docetaxel
Glioma
Carmustine
Survival
Polymers
Gliosarcoma
Therapeutics
Survivors
Neoplasms
Combination Drug Therapy

Keywords

  • Biodegradable polymers
  • Carmustine(BCNU)
  • Combinedinterstitial chemotherapy
  • Docetaxel(Taxotere)
  • Malignantglioma

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neuroscience(all)

Cite this

Interstitial docetaxel (Taxotere), ccarmustine and ccombined interstitial ttherapy : A novel treatment for experimental malignant glioma. / Sampath, Prakash; Rhines, Laurence D.; DiMeco, Francesco; Tyler, Betty M.; Park, Michael C.; Brem, Henry.

In: Journal of Neuro-Oncology, Vol. 80, No. 1, 10.2006, p. 9-17.

Research output: Contribution to journalArticle

Sampath, Prakash ; Rhines, Laurence D. ; DiMeco, Francesco ; Tyler, Betty M. ; Park, Michael C. ; Brem, Henry. / Interstitial docetaxel (Taxotere), ccarmustine and ccombined interstitial ttherapy : A novel treatment for experimental malignant glioma. In: Journal of Neuro-Oncology. 2006 ; Vol. 80, No. 1. pp. 9-17.
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abstract = "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.",
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