High dose chemotherapy for the treatment of malignant brain tumors

Conventional treatment of malignant high grade gliomas includes maximal resection followed by external beam radiotherapy. The addition of adjuvant chemotherapy has provided little improvement in the median duration of survival for these patients, particularly those patients with glioblastoma multiforme. The failure of conventional dose chemotherapy to improve the outcome of patients with high grade brain tumors has led several investigators to utilize high dose chemotherapy in order to overcome the limited benefit seen with conventional dose therapy which is due to intrinsic drug resistance as well as the impermeability of blood brain barrier. The majority of published studies utilizing this approach suggest that the addition of high dose chemotherapy with bone marrow transplant is of marginal benefit. However, most of these trials include small numbers of patients with advanced, refractory disease. A few trials have been reported utilizing high dose therapy in an adjuvant setting and the data from these studies are somewhat more promising. This review will analyze these studies and also discuss possible modifications of this approach in order to improve this aggressive treatment for patients who otherwise would have a dismal prognosis.