Is fulvestrant ("Faslodex") just another selective estrogen receptor modulator?

Over the past two decades, much research has focused on developing new antiestrogens that lack estrogen agonist effects and have improved efficacy and tolerability profiles compared with tamoxifen. As all patients eventually become resistant to tamoxifen, agents that were effective in tamoxifen-resistant disease were also desirable. Currently available SERMs have demonstrated limited tolerability benefits over tamoxifen in terms of their estrogen agonist effects and are also ineffective following tamoxifen failure. Fulvestrant is not "just another SERM," it is the first in a new class of ER antagonists with no agonist effects that binds, blocks, and degrades the ER. As it has a unique mode of action, fulvestrant may offer efficacy and tolerability benefits that have been lacking in the SERMs to date. As fulvestrant reduces cellular ER levels, it limits ER/growth factor receptor cross talk that may delay the onset of endocrine therapy resistance and result in a sustained duration of response. The unique mode of action of fulvestrant and its favorable tolerability profile suggests that it could also be a useful agent in combination treatment regimens. Preclinical data as well as the results of controlled clinical trials have demonstrated that fulvestrant is a novel agent that is distinct from tamoxifen and other SERMs. Ongoing trials will help evaluate more fully the role of fulvestrant in the treatment of hormone-sensitive breast cancer. © 2006, Copyright the Authors.