ESTRAMUSTINE IN MALIGNANT GLIOMA

Estramustine, a carbamate ester combining 17 beta-estradiol and nornit rogen mustard, has primarily been employed in the treatment of advance d prostatic carcinoma. However, a significant amount of preclinical in vestigation has been directed toward estramustine's activity against h uman malignant glioma. These studies have demonstrated that estramusti ne has potent antiproliferative effects against malignant glioma both in vitro and in vivo. Similar antimitotic effects also have been demon strated for other carbamate esters. Estramustine does not impair proli feration of nonneoplastic astrocytes at concentrations that inhibit gl ioma cells. Although the reasons for this selective activity remain to be determined, it has been shown that malignant gliomas expresses an estramustine-specific binding site, estramustine-binding protein, more than brain tissue. In the clinical situation, an uptake and accumulat ion of estramustine in human glioma tissue have been demonstrated. Est ramustine has been shown to enhance the cytotoxic effects of irradiati on in relatively radioresistant glioma cells both in cell culture and in a rat glioma model. Estramustine has been regarded as mainly an ant i-mitotic drug but recently other effects such as inhibition of DNA sy nthesis, induction of apogtosis, and membrane alterations have been sh own. This report summarizes the preclinical observations concerning th e effects of estramustine and related compounds on human malignant gli omas. These findings form the basis for proposing further laboratory a nd clinical investigation regarding estramustine and human malignant g liomas.