Fulvestrant ('
Faslodex') is a new
estrogen receptor (ER) antagonist that has no agonist effects. It binds, blocks and accelerates degradation of the ER, leading to a complete abrogation of
estrogen-sensitive gene transcription. In postmenopausal women with advanced
breast cancer progressing on prior endocrine
therapy,
fulvestrant is at least as effective as the third-generation
aromatase inhibitor (AI)
anastrozole. In this single-center experience, 42 postmenopausal patients with metastatic
breast cancer who had been heavily pretreated with prior endocrine
therapy and
chemotherapy were treated with
fulvestrant. Prior endocrine
therapies included selective ER modulators (including
tamoxifen and
toremifene), AIs,
megestrol acetate, and high-dose
estrogens. In total, eight patients (19%) achieved stable disease (SD) for > or =24 weeks, including two patients with SD for 2 years and one with SD for 14 months.
Fulvestrant was well tolerated with the majority of adverse events related to the site of metastatic disease. These data demonstrate that
fulvestrant is a well tolerated and effective endocrine
therapy for postmenopausal women with metastatic
breast cancer who have been heavily pretreated with prior
therapies. The novel mechanism of action of
fulvestrant reduces the likelihood of cross-resistance with other endocrine
therapies and therefore this agent may be active in patients who have proved to be resistant to treatments such as
tamoxifen or AIs. The use of
fulvestrant earlier in the sequence of endocrine treatments may achieve better responses than observed in this heavily pretreated patient population.