A review of current and future treatment strategies for malignant astrocytomas in adults.
BACKGROUND
For more than 20 years, after establishing the role of postoperative radiotherapy for malignant astrocytomas, no definitive improvement in survival rates could be observed, despite advances in established treatment modalities such as radiotherapy and chemotherapy. This review discusses available laboratory and clinical data as well as recent advances in our knowledge about prognostic factors (Table 1) and their implications for the design of future clinical trials.


RESULTS
Elucidation of the biology of malignant astrocytomas allowed for development of rational new approaches, such as gene therapy and immunotherapy, which could interfere with established treatment regimens or being used independently. Possible strategies include the restoration of defective cancer-inhibitory genes, cell transduction or transfection with antisense DNA corresponding to genes coding for growth factors and their receptors, or with the so-called suicide genes. Several antiangiogenic approaches such as administration of thalidomide, protamine, or monoclonal antibodies against vascular endothelial growth factor have been developed, too. Further treatment possibilities include modulation of drug resistance, e.g. by P-glycoprotein antagonists or O6-alkyl-guanine-DNA-transferase inhibitors, inhibition of matrix metalloproteinases, inhibition of protein kinase C, and administration of agents such as phenylbutyrate or valproic acid that showed promising antiproliferative effects in vitro.


CONCLUSIONS
Several rational new approaches are now entering clinical trials (Table 2). In the light of limited survival after standard treatment it is recommended that patients should be offered participation in such trials.
Nieder
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Department of Experimental Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, USA.
Nestle
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D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001254:Astrocytoma / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D001932:Brain Neoplasms / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D015316:Genetic Therapy; D006801:Humans; D011379:Prognosis; D015996:Survival Rate
D000970:Antineoplastic Agents