High-dose chemotherapy with autologous bone marrow transplantation in the treatment of high grade astrocytomas in adults: therapeutic rationale and clinical experience

Abstract

High-grade astrocytomas are the most common primary malignant brain tumors in adults and constitute a significant cancer problem in the USA accounting for nearly 11,000 deaths annually. Despite improvements in neurosurgical techniques and radiotherapy, the prognosis of these patients remains dismal with median survivals of less than 1 year. Recent data suggest that conventional chemotherapy may be more active in these tumors than previously appreciated but survival has not been substantially altered. Poor drug delivery secondary to the unique neuroanatomical and pathologic constraints of the blood-brain and blood-tumor barrier may contribute to the lack of a significant impact of conventional dose chemotherapy on the natural history of these tumors. In addition, the substantial intratumor cellular heterogeneity invariably found in these tumors undoubtedly contributes to the development of drug resistance. Based on trials of high-dose chemotherapy with autologous bone marrow transplantation (ABMT) in other tumor types, clinical investigators have begun to consider the potential for high-dose chemotherapy to overcome problems of poor drug delivery and cellular drug resistance in brain tumors. In this report, the rationale behind the use of high-dose chemotherapy with ABMT in the treatment of patients with high-grade astrocytomas, and relevant clinical trials conducted to date, are reviewed. Although these trials suggest that survival is not improved in patients treated at the time of relapse, early data suggest that high-dose chemotherapy with ABMT may hold promise as adjuvant treatment in this patient population.