A Phase I-ii Trial of Lovastatin for Anaplastic Astrocytoma and Glioblastoma Multiforme

摘要: Malignant gliomas are thought to be highly dependent on the mevalonate pathway for cell growth. Lovastatin, a cholesterol-lowering drug, inhibits not only rate-limiting step in (hepatic hydroxymethyl glutaryl coenzyme A reductase), but also prenylation of several key regulatory proteins including ras and small guanosine triphosphate binding proteins. Therefore, from August 1994 through March 1996, 18 patients with either anaplastic glioma or glioblastoma multiforme were entered into trial testing safety high-dose lovastatin without radiation. Although response data is too premature evaluate activity, fact that high doses well tolerated concurrent radiation suggests central nervous system toxicity will significant limiting as more selective farnesyltransferase inhibitors brought clinic sensitizers.