Therapeutic strategy for central nervous system tumors: present status, criticism and potential

Surgery, radiotherapy, chemotherapy and immunotherapy represent the combined therapeutic approach to malignant brain tumors. Surgery plays an important role in the treatment of malignant gliomas to ensure a correct diagnosis and to make room within the confines of the skull. Surgery must provide low mortality, low morbidity and at the same time, the most thorough removal possible of the tumor, while respecting the normal brain tissue surrounding the tumor. However, if treatment is limited to surgery alone, only modest results are obtained. The median survival is, in fact, 17 weeks. Radiotherapy for malignant gliomas has been used for 40 years now, but only recently has it been clearly demonstrated that doses lower than 50 Gy "whole brain" are insufficient, as is localized radiation therapy. The addition of radiotherapy (60 Gy whole brain) increases median survival to 37 weeks. The most promising approach to brain tumor therapy in the last decade is chemotherapy. Chemotherapy must take into account drug delivery problems related to the blood brain barrier, the pharmacodynamics of the brain and the cell kinetics of malignant glioma. Many chemotherapeutic substances have been employed in the treatment of brain tumors, but in particular, the nitrosoureas seem to provide the best results. Infact, the addition of BCNU to surgery and radiotherapy produces a median survival of 51 weeks. The immunotherapy of malignant gliomas has been attempted as active specific and non-specific immunotherapy, adoptive and restorative immunotherapy but, until now, the results have been disappointing. The present situation and the potential of combined therapy in the treatment of brain tumors are discussed.