Cytostatic Agents in the Management of Malignant Gliomas.
BACKGROUND: Cytotoxic therapy for malignant gliomas is limited by poor delivery and drug resistance, and local therapy is ineffective in managing migratory cells. However, recent developments in malignant glioma therapy involve trials of cytostatic rather than conventional cytotoxic agents. METHODS: The biology of the brain extracellular matrix, tumor invasion, and angiogenesis are reviewed, and the cytostatic agents that inhibit matrix metalloproteinases, angiogenesis, cell proliferation, and signal transduction are discussed, as well as studies of the angiogenic and migratory capacity of malignant brain tumors. RESULTS: Two specific and interrelated areas, anti-invasion (migration) and anti-angiogenesis, are potential areas to develop new treatment strategies. Tumor invasion and angiogenesis are important components of the spread and biologic effects of malignant gliomas. Several proteinase inhibitors are in clinical trial, as well as anti-angiogenic agents and signal transduction cascade inhibitors. CONCLUSIONS: Biologic control of brain tumor cell populations may offer a new management approach to add to currently available management options for malignant brain tumors.
Mikkelsen
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Henry Ford Midwest Neuro-Oncology Center, Department of Neurosurgery, Detroit, Ml 48202, USA.