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 resea rch leading to the discovery of inhibitors of tumor neovascularization. The therapeutic potential of systemically administered antiangiogenic drugs fo r brain tumors, however, is limited by a variety of anatomic and physiologi c barriers to drug delivery. Implantable controlled-release polymers for lo cal drug administration directly into the tumor parenchyma have therefore b een developed to achieve therapeutic concen-trations of these drugs within the brain while minimizing systemic toxicity. With use of these polymers, s uccessfull antiangiogenic therapy for treatment of experimental intracrania l malignancies has been achieved. This has been demonstrated with a variety of otherwise unrelated drugs - including the angiostatic steroids, tetracy cline derivatives, and amiloride - which modulate collagenase activity, and thus, basement membrane and interstitial matrix metabolism. Controlled-rel ease polymers provide a clinically practicable method of achieving sustaine d antian-giogenic therapy which can be readily used in combination with oth er treatment modalities such as cytoreductive surgery, radiation, and cytot oxic chemotherapy.