Biodegradable polymer implants to treat brain tumors

Henry Brem, P. Gabikian

Research output: Contribution to journalArticle

Abstract

We have developed a systematic approach for the discovery and evaluation of local treatment strategies for brain tumors using polymers. We demonstrated the feasibility of polymer-mediated drug delivery by using the standard chemotherapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and showed that local treatment of gliomas by this method is effective in animal models of intracranial tumors. This led to clinical trials for glioma patients, and subsequent approval of Gliadel™ [(3.8% BCNU): p(CPP:SA)] by the FDA and other worldwide regulatory agencies. Twenty-two additional clinical trials are currently underway evaluating other issues related to the BCNU polymer, such as dosage, combination with systemic treatments, and combination with various forms of radiation and resistance modifiers. These trials are a result of laboratory investigations using brain tumor models; based on these models, other research groups have initiated clinical trials with novel combinations of different drugs and new polymers for both intracranial tumors (5-fluorouracil delivered via poly(D-L lactide-co-glycolide) polymer) and for tumors outside the brain (paclitaxel in PPE microspheres for ovarian cancer). Since only 1/3 of patients with glioblastoma multiforme (GBM) are sensitive to BCNU, the need to search for additional drugs continues. Although we are attacking major resistance mechanisms, there still will be tumors that do not respond to BCNU therapy but are sensitive to agents with different mechanisms of action, such as taxanes, camptothecin, platinum drugs, and antiangiogenic agents. Thus, it is necessary to explore multiple single agents and ultimately to combine the most effective agents for the clinical treatment of GBM. Furthermore, multimodal approaches combining radiotherapy with microsphere delivery of cytokines and antiangiogenic agents have demonstrated encouraging results.

Original languageEnglish (US)
Pages (from-to)63-67
Number of pages5
JournalJournal of Controlled Release
Volume74
Issue number1-3
DOIs
StatePublished - Jul 6 2001

Fingerprint

Absorbable Implants
Carmustine
Brain Neoplasms
Polymers
Angiogenesis Inhibitors
Clinical Trials
Glioblastoma
Microspheres
Glioma
Pharmaceutical Preparations
Therapeutics
Taxoids
Camptothecin
Neoplasms
Drug Combinations
Paclitaxel
Platinum
Fluorouracil
Ovarian Neoplasms
Radiotherapy

Keywords

  • BCNU
  • Brain tumor
  • Glioma
  • Implantable polymer
  • Local drug delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Biodegradable polymer implants to treat brain tumors. / Brem, Henry; Gabikian, P.

In: Journal of Controlled Release, Vol. 74, No. 1-3, 06.07.2001, p. 63-67.

Research output: Contribution to journalArticle

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