Fulvestrant.

Abstract

Fulvestrant is a 7alpha-alkylsulphinyl analogue of estradiol that competes with endogenous estrogen for binding to the estrogen receptor. Once bound to the receptor, fulvestrant attenuates receptor dimerisation, effecting a rapid degradation of the estrogen receptor protein and inhibition of transcription. Fulvestrant is a potent inhibitor of the growth of human breast cancer cells in vitro and in vivo. It has demonstrated pure anti-estrogenic activity in animal systems. Intramuscular fulvestrant 250 mg once a month was as effective as the oral aromatase inhibitor anastrozole 1 mg/day in 2 phase III trials in postmenopausal women with advanced breast cancer who had received prior endocrine therapy. Median time to disease progression (the primary end-point) with fulvestrant and anastrozole was 5.4 and 3.4 months (North American trial) and 5.5 and 5.1 months (European trial). The median duration of response was 19.3 and 10.5 months (North American trial) and 14.3 and 14.0 months (European trial). The most common adverse events with fulvestrant are gastrointestinal disturbances and hot flushes. Fulvestrant showed similar tolerability to anastrozole in 2 phase III trials.