Local anti-angiogenic brain tumor therapies.

The critical role of angiogenesis in the growth of solid tumors, including neoplasms of the central nervous system, has provided the impetus for research leading to the discovery of inhibitors of tumor neovascularization. The therapeutic potential of systemically administered antiangiogenic drugs for brain tumors, however, is limited by a variety of anatomic and physiologic barriers to drug delivery. Implantable controlled-release polymers for local drug administration directly into the tumor parenchyma have therefore been developed to achieve therapeutic concentrations of these drugs within the brain while minimizing systemic toxicity. With use of these polymers, successful antiangiogenic therapy for treatment of experimental intracranial malignancies has been achieved. This has been demonstrated with a variety of otherwise unrelated drugs -- including the angiostatic steroids, tetracycline derivatives, and amiloride -- which modulate collagenase activity, and thus, basement membrane and interstitial matrix metabolism. Controlled-release polymers provide a clinically practicable method of achieving sustained antiangiogenic therapy which can be readily used in combination with other treatment modalities such as cytoreductive surgery, radiation, and cytotoxic chemotherapy.