Pharmacotherapy of malignant astrocytomas of children and adults - Currentstrategies and future trends

This article reviews the conceptual progression in the pharmacological ther apy of malignant astrocytoma (MA) over the past decade, and its future tren ds. It is a selective rather than an exhaustive inventory of literature cit ations. The experience of the Brain Tumour Cooperative Group (BTCG) and ear lier phase III trials are summarised to place subsequent phase II and I stu dies of single and combination agent chemotherapy in perspective. The BTCG experience of the 1970s to 1980s may be summarised to indicate tha t external beam radiotherapy (EBRT) is therapeutic, although not curative, and not further improved upon by altering fractionation schedules, or the a ddition of radioenhancers. Whole brain and reduced whole brain EBRT with fo cal boost were comparable regimens. Nitrosourea-based, adjuvant chemotherap y provided a modest improvement in survival among adult patients, which was comparable with that of other single drugs or multidrug regimes. The multi agent schedules, however, had a correspondingly higher toxicity rate. Intra -arterial administration was associated with significant risk, which confer red no therapeutic advantage. The trend of the past decade has been towards multiagent chemotherapy altho ugh its benefit cannot be predicted from the classic prognostic factors. Pu blished experience with investigational trials utilising myeloablative chem otherapy with autologous bone marrow or peripheral blood stem cell haemopoi etic support, drug delivery enhancement methods and radiosensitisers is cri tically reviewed. None of these approaches have achieved wide-spread accept ance in the treatment of adult patients with MA. Greater attention is place d on recent 'chemoradiotherapy' trials, which attempt to integrate and maxi mise the cytoreductive potential of both modalities. This approach holds pr omise as an effective means to delay or overcome the evolution of tumour re sistance, which is probably one of the dominant determinants of prognosis. However, the efficacy of this approach remains unproven. New chemotherapeut ic agents as well as biological response modifiers, protein kinase inhibito rs, angiogenesis inhibitors and gene therapy are also discussed; their role in the therapeutic armamentarium has not been defined.