Chemotherapy for brain tumors

Brain tumors are the second and fourth leading causes of cancer mortality in children and in young adults between the age of 15 and 34 respectively. Clinical progress in the treatment of these malignancies has been slow. Surgery is difficult because tumor cells infiltrate into surrounding brain, making complete resection impossible. Physical localization of the tumor in deep cortex or in highly functional areas is also a problem. Radiotherapy is limited by low brain tolerance and by the infiltration of tumor cells into normal brain. Adjuvant chemotherapy is thus essential to the treatment of some types of brain tumors. Response to chemotherapy depends on the concentration of drugs reaching the tumor, blood flow inside the tumor, inherent or acquired drug resistance of the cancer and integrity of the blood-brain barrier (BBB).

The role of the BBB in resistance to chemotherapy of brain tumors remains unclear and controversial (Tomita, 1991; Lesser and Grossman, 1993; Stewart, 1994; Conrad et al., 1995). The main argument in favor of an active role is the fact that most chemotherapeutic agents achieve only low concentrations in the brain and that lipophilic agents crossing the BBB are those producing an increase, although modest, in median survival of patients.