For patients with nonresectable glioblastoma (GB) or recurrent GB, we have recently been using an interstitial chemotherapy with biodegradable polylactic acid pellets containing nimustine chloride (ACNU), in combination with superselective arterial ACNU injection, routine irradiation and chemotherapy. The ACNU pellets are prepared by mixing polylactic acid powder and ACNU, and then melting the mixture at low temperature and moulding it into a thin pellet. Pharmacological anticancer activity was experimentally demonstrated by the finding that a region of suppression was present surrounding an ACNU pellet placed in a B6 melanoma cell culture disc, but that no such suppression was present around a control pellet. In order to determine the spatial and temporal distribution of ACNU, a small pellet (ACNU: 0.6 mg) was implanted in the frontal lobe of rats. ACNU concentration determined by HPLC was 61.0 µ/g brain tissue on day 1. 22.5 on day 3, and 5.5 on day 7; small amounts of ACNU were in fact released for at least 4 weeks after implantation. This pellet was used for the clinical treatment of 11 GB patients. Four patients had several pieces of pellets implanted immediately after CT-guided stereotactic biopsy, and the other 7 had pellets placed in residual tumor after partial removal at craniotomy. No ACNU was detectable in serum. CT studies obtained at subsequent appropriate intervals disclosed gas formation around the pellets, a slight increase in edema, and necrosis or decrease in CT enhancement of tumor beginning around day 12 after implantation. Bone marrow suppression did not occur, since ACNU was administered interstitially and in the range of 50–200 mg (average: 126 mg) per patient. Most patients underwent other modalities of antitumor treatment 2 or 3 weeks after implantation. Although the median survival time (MST) for all patients was 21 weeks, and thus not favorable, about half of those treated were old, and half of the tumors treated were located in midline structures. However, the MST for hemispheric GB patients was more favorable than that for midline tumors (47 vs. 17 weeks). There was no significant difference in survival time between the group of patients with stereotactic implantation and the group subjected to craniotomy. In conclusion, a large dose of ACNU can be implanted locally without systemic side effects using biodegradable, slowly releasing pellets. This type of treatment is thus an additional option in the treatment of malignant brain tumors.

Keywords:
ACNU, Glioblastoma, Drug delivery system, Lactic acid polymer, Brain tumor, Chemotherapy
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© 1994 S. Karger AG, Basel
1995
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