Role of high-dose chemotherapy with hemopoietic stem-cell support in the treatment of adult patients with high-grade glioma

Despite surgery, post-operative irradiation and adjuvant conventional chemo therapy, prognosis of high-grade gliomas remains poor. Carmustine (BCNU) ha s been shown to have limited activity at conventional dosage bast is still the standard chemotherapy. Activity of chemotherapy is limited by the blood -brain barrier impermeability and high levels of expression of multidrug re sistance proteins on tumor and/or endothelial cells. Despite high response rates, development of intra-arterial chemotherapy remains limited because o f frequent acute brain toxicity related to drug administration. High-dose i ntravenous chemotherapy rescued by autologous hemopoietic stem cell transpl antation is an alternative that might increase drug delivery through the bl ood-brain barrier and tumor control. Several phase I-II trials using high-d ose BCNU were published. The maximum tolerated dose seems to be 800 mg/m(2) and interstitial pneumonitis and hepatitis are dose-limiting toxicities. F ew phase I-II trials of high-dose therapy were published using drug combina tions. High response rates in patients with progressive tumor were observed and in adjuvant setting, encouraging results in terms of median survival t ime and long survivors were published. No phase III trial was reported to d ate. Future investigations should include randomized trials comparing high- dose and conventional-dose chemotherapy and development of new high-dose re gimens that incorporate new drugs such as temozolomide.