Injection of Chemotherapeutic Microspheres and Glioma III: Parameters to Optimize Efficacy

Authors: Emerich, D.F.1; Winn, S.R.2; Bartus, R.T.1

Source: Cell Transplantation, Volume 11, Number 1, 2002 , pp. 35-45(11)

Publisher: Cognizant Communication Corporation

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Abstract:

Injectable microspheres may provide a means of providing local, sustained exposure of glioma to chemotherapeutics to improve patient survival. Using a rodent model of surgically resected glioma, we previously demonstrated that direct injections of chemotherapeutic microspheres into the tissue surrounding a resection cavity provide superior survival effects over injections of the same microspheres directly into the surgical cavity. The present experiments extended this novel observation by exploring several parameters related to the use of intraparenchymal injections of chemotherapeutic microspheres to treat glioma. Using a rat model of resected glioma, several principles regarding the use of local sustained release carboplatin microspheres were established. First, an inverted U dose–response was observed, wherein further dose escalation beyond the optimal dose was not efficacious and indeed produced significant local toxicity. Second, it was necessary to expose approximately 40% of the tumor margin to sustained release carboplatin in order to increase survival in this model. Survival was not enhanced when the proportion of the tumor margin exposed to carboplatin was only 20%. Third, the distribution of the chemotherapeutic microsphere injections along the tumor perimeter was shown to be important, requiring that the entire perimeter be proportionately exposed to the chemotherapeutic agent. Together, these data continue to support the development of chemotherapeutic microspheres for treating glioma. However, they also caution that a number of fundamental parameters can profoundly influence the efficacy that might be expected from local sustained delivery. Careful attention to these principles is not only required if chemotherapeutic microspheres are to be used efficaciously, but these principles should provide a foundation to further optimize the potential of this and other polymeric delivery systems under development for local, intraparenchymal drug delivery to glioma.

Keywords: Key words: Glioma; Microsphere;; Sustained release

Document Type: Research Article

DOI: http://dx.doi.org/10.0000/096020198389762

Affiliations: 1: *Alkermes, Inc., Cambridge, MA 02139 2: †Department of Surgery, OHSU, Portland, OR 97201

Publication date: January 1, 2002

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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