Interstitial Docetaxel (Taxotere), Carmustine and Combined Interstitial Therapy: a Novel Treatment for Experimental Malignant Glioma

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 and rat brain-tumor 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 antiglioma therapy and that the combination of drug regimens via biodegradable polymers may be a great therapeutic benefit to patients with malignant glioma.

Core/shell microspheres via coaxial electrohydrodynamic atomization for sequential and parallel release of drugs

“…Herein, each factor requires different time scales and concentration profiles because of the nature of the repair/inhibition process. This suggests that the sequential or coupled release of multiple factors with different temporal profiles will become essential and critical for a successful tissue regeneration or tumor inhibition strategy 1–12. However, in modern design, most delivery systems only accounts for a single factor, limiting the overall efficacy of the therapy 13–19.…”

Polifeprosan 20, 3.85% carmustine slow release wafer in malignant glioma: patient selection and perspectives on a low-burden therapy

“…For example, when inulin, a large molecule that has less potential to cross the blood–brain barrier, is administered by wafer technology, the inulin persists in the brain for a longer period of time and diffuses a larger distance from the brain/polymer interface. The feasibility of polifeprosan 20 polymer as a slow release delivery technology for alternative therapeutic agents has been demonstrated in preclinical models using paclitaxel,60 IUDR,61,62 temozolomide,63 taxotere64 camptothecin,65,66 tiripazamine,67 and other agents. When more effective agents are identified, this may be considered again.…”

Interstitial Chemotherapy for Malignant Gliomas

“…In addition, various chemotherapeutic agents other than BCNU have been exploited to deliver through polymeric system. Preclinical studies demonstrated that many drugs such as temozolomide, paclitaxel, taxotere, and camptothecin were efficacious against gliomas through polymeric delivery (46)(47)(48)(49). Further clinical investigation of the safety and efficacy is therefore warranted.…”