Pharmacotherapy of malignant astrocytomas of children and adults: current strategies and future trends.

This article reviews the conceptual progression in the pharmacological therapy of malignant astrocytoma (MA) over the past decade, and its future trends. It is a selective rather than an exhaustive inventory of literature citations. The experience of the Brain Tumour Cooperative Group (BTCG) and earlier phase III trials are summarised to place subsequent phase II and I studies of single and combination agent chemotherapy in perspective. The BTCG experience of the 1970s to 1980s may be summarised to indicate that external beam radiotherapy (EBRT) is therapeutic, although not curative, and not further improved upon by altering fractionation schedules, or the addition of radioenhancers. Whole brain and reduced whole brain EBRT with focal boost were comparable regimens. Nitrosourea-based, adjuvant chemotherapy provided a modest improvement in survival among adult patients, which was comparable with that of other single drugs or multidrug regimes. The multiagent schedules, however, had a correspondingly higher toxicity rate. Intra-arterial administration was associated with significant risk, which conferred no therapeutic advantage. The trend of the past decade has been towards multiagent chemotherapy although its benefit cannot be predicted from the classic prognostic factors. Published experience with investigational trials utilising myeloablative chemotherapy with autologous bone marrow or peripheral blood stem cell haemopoietic support, drug delivery enhancement methods and radiosensitisers is critically reviewed. None of these approaches have achieved wide-spread acceptance in the treatment of adult patients with MA. Greater attention is placed on recent 'chemoradiotherapy' trials, which attempt to integrate and maximise the cytoreductive potential of both modalities. This approach holds promise as an effective means to delay or overcome the evolution of tumour resistance, which is probably one of the dominant determinants of prognosis. However, the efficacy of this approach remains unproven. New chemotherapeutic agents as well as biological response modifiers, protein kinase inhibitors, angiogenesis inhibitors and gene therapy are also discussed; their role in the therapeutic armamentarium has not been defined.