Chemotherapy and delivery in the treatment of primary brain tumors

Malignant astrocytomas are aggressive neoplasms with a dismal prognosis despite optimal treatment. Maximal resective surgery is traditionally complemented by radiation therapy. Chemotherapy is typically used on patients with tumor recurrence, when their functional status is congruent with further treatment. The classic agents used are nitrosoureas, but temozolomide is gradually taking a more prominent role recently. New agents, biological modifiers, are increasingly used in clinical trials in an effort to affect the intrinsic biologic aberrations harboured by tumor cells. These drugs comprise differentiation agents, anti-angiogenic agents, matrix-metalloproteinase inhibitors and signal transduction inhibitors, among others. The issue of chemotherapy delivery is also crucial. Classically, agents are administered either intravenously or orally. In an effort to circumvent the obstacle imposed by the blood-brain barrier, investigators are actively working on more invasive methods of delivery, namely intra-arterial infusion with or without blood-brain barrier disruption or direct intra-cerebral administration, with clysis or drug-impregnated wafers. This article reviews the standard cytotoxic agents that have been used to treat malignant astrocytomas, and the different combination regimen offering promise. In addition, recent advances with biological modifiers are also discussed, along with alternate methods to deliver the agents more efficiently across the blood-brain barrier.