University of Nottingham, Nottingham University Hospitals, Nottingham, UK.
Curr Med Chem. 2010;17(10):902-14. doi: 10.2174/092986710790820633.
Fulvestrant is a novel endocrine therapy for breast cancer, with a unique structure and mode of action. It binds competitively to the oestrogen receptor (ER), with high affinity, and downregulates ER by functional blockade and increased turnover. Fulvestrant has reached the clinic via extensive pre-clinical and clinical trials, which demonstrated fulvestrant's unique characteristics and showed that they translate to equivalent or improved clinical efficacy compared to established endocrine agents. Fulvestrant is currently licensed for use in postmenopausal women with hormone receptor positive advanced breast cancer which has progressed on prior endocrine therapy. As a pure oestrogen antagonist, fulvestrant avoids the risk of detrimental side effects of selective ER modulators such as tamoxifen, which has partial agonist activity. Fulvestrant, the only parenteral agent in this setting, has a good side effect profile and is well tolerated. Due to its unique mode of action, fulvestrant lacks cross-resistance with existing agents. Fulvestrant is the subject of much ongoing research, which utilises knowledge of its novel mechanism and pharmacokinetic profile in order to optimise clinical efficacy and explore new roles, including first-line use in advanced breast cancer, use in combination with existing agents, in males, and in premenopausal women, and use as an adjuvant therapy.
氟维司群是一种新型的乳腺癌内分泌治疗药物，具有独特的结构和作用模式。它与雌激素受体（ER）竞争性结合，具有高亲和力，并通过功能阻断和增加周转率来下调 ER。氟维司群通过广泛的临床前和临床试验进入临床，这些试验证明了氟维司群的独特特征，并表明与已确立的内分泌药物相比，其具有等效或改善的临床疗效。氟维司群目前被批准用于绝经后妇女的激素受体阳性晚期乳腺癌，这些患者在先前的内分泌治疗中已经进展。作为一种纯雌激素拮抗剂，氟维司群避免了选择性 ER 调节剂（如他莫昔芬）的有害副作用风险，他莫昔芬具有部分激动剂活性。氟维司群是该领域唯一的注射用药物，具有良好的副作用谱且耐受性良好。由于其独特的作用模式，氟维司群与现有药物之间缺乏交叉耐药性。氟维司群是许多正在进行的研究的主题，这些研究利用其新型机制和药代动力学特征来优化临床疗效，并探索新的作用，包括在晚期乳腺癌中的一线应用、与现有药物联合应用、在男性和绝经前妇女中的应用，以及作为辅助治疗。
