Development of a Pure Antiestrogen Fulvestrant

Clinical experience with the nonsteroidal antiestrogen tamoxifen hasestablished unequivocally the value of antiestrogen therapy in the treatment ofpatients with breast carcinoma. But tamoxifen-like drugs have estrogen-like actionson certain tissues and their intrinsic partial-agonist effects may have undesiredconsequences, such as increased endometrial proliferation, a slightly increased riskof endometrial carcinoma. A new class of specific antiestrogen without any agonisteffects may have advantages over tamoxifen in the treatment of patients withestrogen dependent disease. The search for such a drug revealed a number ofcompounds with the appropriate effect, of which fulvestrant (ICI l82780,AstraZeneca) was selected for clinical evaluation because of its greater potencyand affinity for the estrogen receptor (ER). In this paper, we reviewed the mode ofaction of fulvestrant, preclinical data, clinical data and clinical uses.