Interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas

Henry Brem, M. S. Mahaley, N. A. Vick, K. L. Black, S. C. Schold, P. C. Burger, A. H. Friedman, I. S. Ciric, T. W. Eller, J. W. Cozzens, J. N. Kenealy

Research output: Contribution to journalArticle

Abstract

Malignant gliomas have been difficult to treat with chemotherapy. The most effective agent, BCNU (carmustine), has considerable systemic toxicity and a short half-life in serum. To obviate these problems, a method has been developed for the local sustained release of chemotherapeutic agents by their incorporation into biodegradable polymers. Implantation of the drug-impregnated polymer at the tumor site allows prolonged local exposure with minimal systemic exposure. In this Phase I-II study, 21 patients with recurrent malignant glioma were treated with BCNU released interstitially by means of a polyanhydride biodegradable polymer implant. Up to eight polymer wafers were placed in the resection cavity intraoperatively, upon completion of tumor debulking. The polymer releases the therapeutic drug for approximately 3 weeks. Three increasing concentrations of BCNU were studied; the treatment was well tolerated at all three levels. There were no adverse reactions to the BCNU wafer treatment itself. The average survival period after reoperation was 65 weeks for the first dose group, 64 weeks for the second dose group, and 32 weeks for the highest dose group. The overall mean survival time was 48 weeks from reoperation and 94 weeks from the original operation. The overall median survival times were 46 weeks postimplant and 87 weeks from initial surgery. Eighteen (86%) of 21 patients lived more than 1 year from the time of their initial diagnosis and eight (38%) of 21 patients lived more than 1 year after intracranial implantation of the polymer. Frequent hematology, blood chemistry, and urinalysis tests did not reveal any systemic effect from this interstitial chemotherapy. Since the therapy is well tolerated and safe, a placebo-controlled clinical trial has been started. The trial will measure the effect of the second treatment dose on survival of patients with recurrent malignant glioma.

Original languageEnglish (US)
Pages (from-to)441-446
Number of pages6
JournalJournal of Neurosurgery
Volume74
Issue number3
StatePublished - 1991

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Keywords

  • BCNU
  • Biodegradable polymer
  • Brain neoplasm
  • Chemotherapy
  • Drug delivery
  • Glioma

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Brem, H., Mahaley, M. S., Vick, N. A., Black, K. L., Schold, S. C., Burger, P. C., Friedman, A. H., Ciric, I. S., Eller, T. W., Cozzens, J. W., & Kenealy, J. N. (1991). Interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas. Journal of Neurosurgery, 74(3), 441-446.