A review of current and future treatment strategies for malignant astrocytomas in adults

Background: For more than 20 years, after establishing the role of postoper ative radiotherapy for malignant astrocytomas, no definitive improvement in survival rates could be observed, despite advances in established treatmen t modalities such as radiotherapy and chemotherapy. This review discusses a vailable laboratory and clinical data as well as re cent advances in our kn owledge about prognostic factors (Table 1) and their implications for the d esign of future clinical trials. Results: Elucidation of the biology of malignant astrocytomas allowed for d evelopment of rational new approaches, such as gene therapy and immunothera py, which could interfere with established treatment regimens or being used independently. Possible strategies include the restoration of defective ca ncer-inhibitory genes, cell transduction or transfection with antisense DNA corresponding to genes coding for growth factors and their receptors, or w ith 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 treatm ent possibilities include modulation of drug resistance, e.g. by P-glycopro tein antagonists or O6-alkyl-guanine-DNA-transferase inhibitors, inhibition of matrix metalloproteinases, inhibition of protein kinase C: and administ ration of agents such as phenylbutyrate or valproic acid that showed promis ing antiproliferative effects in vitro. Conclusions: Several rational new approaches are now entering clinical tria ls (Table 2). In the light of limited survival after standard treatment it is recommended that patients should be offered participation in such trials .