Advances in chemotherapy for brain tumors

In recent years, there has been increasing evidence that chemotherapy has a role in the treatment of patients with NHL-CNS, medulloblastoma, anaplastic oligodendroglioma, certain malignant pineal region tumors, and ependymomas. Although adjuvant chemotherapy produces a modest benefit in patients with malignant gliomas, overall progress in the treatment of these tumors has been disappointing. Significant problems remain with improving drug delivery and overcoming drug resistance. Because surgery is unlikely to be curative for infiltrating malignant gliomas, and radiation therapies have been maximized, the hope for real improvement in survival for these patients rests largely with advances in medical therapies such as the development of new drugs and improved methods of delivery (other innovative therapies such as gene delivery are discussed elsewhere in this issue). High-dose chemotherapy with autologous bone marrow transplantation has real potential if toxicity issues can be resolved. Interstitial chemotherapy and intra-arterial infusion with BBB disruption may also hold promise for selected groups of patients. Many cytokines have antitumor activity and may be combined with standard chemotherapeutic agents in chemo-bio protocols. Further advances, however, will depend on improved understanding of the molecular and cellular biology of these tumors. As our knowledge of the mechanisms of drug resistance increases, it may be possible to design more-effective drugs that overcome these mechanisms. Similarly, progress in our understanding of the role of specific oncogenes in tumorigenesis may allow drugs targeting oncogenes and their protein products to be developed.