Recent advances in brain tumor therapy: local intracerebral drug delivery by polymers.
New approaches to malignant glioma are being actively investigated. Local drug delivery directly to the site of the tumor is one novel approach that has been approved by the US FDA and other regulatory agencies worldwide. This agent, Gliadel, delivers the chemotherapeutic drug carmustine (BCNU) from a biodegradable polymer placed in the resection cavity after brain tumor surgery. Gliadel represents the first clinical application of polymer delivery for brain tumors, but the potential for this new methodology is far greater. In this review, we will briefly summarize the development of Gliadel from a laboratory idea to its current role as an approved treatment for gliomas. Then we will present the most recent work being done to expand the potential benefits of polymeric delivery for brain tumors. This work includes trials for its use as the initial therapy for gliomas, as well as its use against metastasis. Further clinical trials exploring the maximum-tolerated dose and the combination of Gliadel with systemic chemotherapeutic treatments such as temozolamide and O(6)-benzylguanine will be reviewed. Finally, we will present preclinical work on the efficacy of polymeric methods for delivering other chemotherapeutic agents, and a variety of novel compounds that modify brain tumor biology. This latter work represents potential future clinical applications of local polymeric drug delivery to the brain and other sites where cancers can occur.
Guerin
Christopher
C
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Olivi
Alessandro
A
Weingart
Jon D
JD
Lawson
H Christopher
HC
Brem
Henry
H
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002330:Carmustine / Q000008:administration & dosage* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003652:Decanoic Acids; D004337:Drug Carriers; D005910:Glioma / Q000188:drug therapy* / Q000556:secondary; D006801:Humans; D007322:Instillation, Drug; D020714:Maximum Tolerated Dose; D009364:Neoplasm Recurrence, Local; D011091:Polyesters; D013678:Technology, Pharmaceutical
D018906:Antineoplastic Agents, Alkylating; D003652:Decanoic Acids; D004337:Drug Carriers; D011091:Polyesters; C055401:decanedioic acid-4,4'-(1,3-propanediylbis(oxy))bis(benzoic acid) copolymer; D002330:Carmustine