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Glial tumors--new approaches in chemotherapy. (Pharmacology Update).

Article Excerpt
Primary brain tumors (PBT) originate from structures and cells within the brain and are classified according to the presumed cells of origin. Glial tumors, representing 65% of all primary central nervous system (CNS) tumors, are the most common primary brain tumor in adults and arise from glial cells (Bozik & Gilbert, 1994). Chemotherapeutic treatment of primary brain tumors has focused on malignant gliomas, including anaplastic astrocytomas, anaplastic oligodendrogliomas, and glioblastoma multiforme (GBM), largely as a result of the increasing numbers of these tumors being diagnosed and the fatal nature of these tumor types. Conventional therapy at diagnosis is typically maximal been used primarily in a postradiation (or adjuvant) setting or for recurrent disease. Recently, several new classes of agents have been discovered that target specific cellular processes required for cellular division. In addition, an organized approach to evaluation of new approaches has been designated. This article reviews agents and approaches currently being used in the treatment of gliomas as well as the role of National Cancer Institute's NCI consortia.

NIH-Designated Brain Tumor Consortia

To improve the quality of patient care and evaluate the pharmacokinetics of new agents, the NCI has funded two nationwide consortia to conduct Phase I and II clinical trials for persons with brain tumors. Clinical centers that participate in the consortia are given access to new and promising agents from NCI. The names and Web site addresses of the two consortia are New Approaches to Brain Tumor Treatment (NABTT; www.nabtt.org) and North American Brain Tumor Coalition (NABTC; www.nabtc.org). Table 1 provides a brief description of the goals of Phase I, Il, and III trials. Clinical trials conducted through the consortia will test promising new treatment strategies, routes of drug administration, and clinical trial design for the treatment of primary malignancies of the central nervous system.

Each consortium comprises brain tumor centers within various university medical centers throughout the country, which have dedicated clinical and laboratory teams. According to the NABTT Web site, these institutions offer (a) a large adult patient population with primary brain tumors; (b) expert multidisciplinary clinical teams caring for these patients; (c) extensive clinical and laboratory resources; (d) a striking number of ongoing high-quality, clinically relevant, peer-reviewed, and National Institutes of Health (NIH)-funded clinical and laboratory brain tumor research projects; (e) nationally recognized expertise in oncology, pharmacology, and new drug development Phase I and II clinical trials and neurosurgery and neuropathology departments; and (f) extensive expertise in biostatistics, data management, and the coordination of multi-institutional studies. Aligning these organizations within a consortium adds to these strengths a well-defined organizational structure and emphasis on clinical trial design, protocol development, quality control, study monitoring, and data management and analysis. New therapies from the pharmaceutical industry and the NCI can quickly be evaluated through these consortia (NABTT, 2002).

Chemotherapeutic Agents

Classic chemotherapy is cytotoxic and designed to destroy tumor cells by interfering with cell division. There are several factors associated with CNS tumors that may affect the ability to treat these tumors with...

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