Role Of Fulvestrant Research Articles

Fulvestrant alleviates cisplatin-induced acute kidney injury via repression of BNIP3-mediated apoptosis and autophagy.

Cisplatin-induced acute kidney injury (AKI) is a clinical disease characterized by a sudden loss of renal function within a few hours or days, due to cisplatin uptake. Fulvestrant is an oestrogen receptor alpha (ERα) antagonist used for endocrine therapy. However, the role of fulvestrant in cisplatin-induced AKI remains unclear. In this study, we investigated the effects of fulvestrant on the regulation of apoptotic cell death and autophagic response in cisplatin-induced AKI. The human kidney proximal tubule epithelial cell line (HK-2) was co-treated with fulvestrant and cisplatin. C57BL/6 mice were subcutaneously injected with fulvestrant and cisplatin was administered via intraperitoneal injection. First, cisplatin treatment increased ERα expression, apoptosis, and autophagy in HK-2 cells. Fulvestrant treatment decreased apoptosis and autophagy, which were accompanied by cisplatin treatment in HK-2 cells. Consistent with in vitro results, cisplatin treatment significantly increased ERα expression in vivo. Additionally, cisplatin treatment increased renal injury, apoptosis, and autophagy. Surprisingly, compared to that in the cisplatin-treated mice group, reduced cisplatin-induced renal injury, apoptosis, and autophagy was observed in the cisplatin+fulvestrant-treated mice group. In summary, these results suggest that fulvestrant plays an important role in cisplatin-induced AKI by decreasing apoptosis and autophagy.

Role of fulvestrant in the treatment of postmenopausal metastatic breast cancer patients

ABSTRACTIntroduction: Endocrine therapy is considered the cornerstone treatment for postmenopausal women with hormone-receptor positive metastatic breast cancer. Fulvestrant is a selective estrogen receptor down-regulator (SERD) with demonstrated activity and efficacy in the treatment of these patients.Areas covered: The present manuscript aims to review the mechanism of action of fulvestrant, the clinical efficacy data with the use of different dosages and schedules, and finally its role in association with other medications.Expert commentary: Fulvestrant is an active compound with an excellent safety profile for the treatment of women with hormone receptor-positive metastatic breast cancer, The combination of fulvestrant with targeted agents showed increased efficacy and is expected to become a new standard treatment. Results of two clinical trials (i.e. the FALCON and FEVEX trials) are awaited to better clarify the place of fulvestrant in the armamentarium of the available therapies for the treatment of hormone receptor-positive metastatic breast cancer.

The Role of Fulvestrant in the Treatment of Metastatic Breast Cancer: A Case Report

Nowadays we cannot find a cancer, in which the targeted therapy based on targeted diagnostics (immunohistochemistry, FISH, etc.) would not stand in the centre of the investigations. Breast cancer is not an exception either. Although the optimally performed surgery and the adequately planned radiotherapy are still important elements in the treatment of breast cancer and the achievement of effective local tumor control but their role has essentially changed in the last few years. In the treatment of patient who has been suffering from breast cancer for years either with or without his/her knowledge, the surgery should not be performed as soon as possible but when the patient “benefits” the most from this procedure. If distant metastases are present the removal of the tumor from the breast which means only the tip of the iceberg is absolutely unnecessary or it is required only in special cases. Systemic tumor control can be reached only by medicinal treatment. Regarding these treatments the importance of endocrine therapies (antiestrogens, aromatase inhibitors, LH-RH analogues etc.) traditional and modern chemotherapies (antracyclines, taxanes, platinum and pyrimidine derivatives, eribulin etc.) and the targeted biological therapies (trastuzumab, lapatinib, bevacizumab, olaparib etc.) can be emphasized. The targets of these biological therapies are either extracellular or intracellular molecular targets, such as estrogen receptor (tamoxifen, anastrazole, letrozole, exemestane, fulvestrant etc.) HER2 (trastuzumab, lapatinib, etc.), VEGF (bevacizumab, etc.) PARP (olaparib). It is well-known that due to frequent hormone sensitivity of breast cancer drugs influencing the hormonal effect are very effective. From these the importance of fulvestrant is discussed in our article. Based on literature data fulvestrant proved to be efficient both in locally advanced and metastatic breast cancers even if it was administered not as first (or second) line therapy.

Paradigm of polyendocrine therapy in endocrine responsive breast cancer: the role of fulvestrant.

Endocrine therapy is the cornerstone of any treatment plan for endocrine-responsive breast cancer in both the adjuvant and metastatic settings (1). In the metastatic setting in post-menopausal patients aromatase inhibitors (AIs; anastrozole, exemestane, letrozole) are standard therapies, shown to demonstrate improved progression-free survival (PFS) and a favorable adverse effect (AE) profile compared to other endocrine agents such as tamoxifen (2,3).

Nursing Perspectives on Fulvestrant for the Treatment of Postmenopausal Women With Metastatic Breast Cancer

Fulvestrant is an estrogen receptor antagonist indicated for the treatment of hormone receptor-positive metastatic breast cancer (MBC) in postmenopausal women with disease progression following antiestrogen therapy. Fulvestrant has a different mechanism of action than other hormonal therapies, including aromatase inhibitors and tamoxifen. In clinical trials of postmenopausal women with MBC, fulvestrant was effective and well tolerated compared to anastrozole after failure of tamoxifen. The monthly injection regimen of fulvestrant provides nurses with an additional opportunity to improve patient adherence to hormonal therapy, reinforce patient education, and monitor side effects. Several ongoing trials will elucidate the role of fulvestrant in the treatment of MBC. Issues that are being addressed in those trials include alternative doses and schedules, efficacy and safety in other patient populations, and the development of novel treatment combinations. This article provides oncology nurses with the knowledge needed to educate patients on the use of fulvestrant, to effectively administer this medication, and to prevent and manage potential side effects.

Role of fulvestrant in the management of postmenopausal breast cancer

Fulvestrant is a form of endocrine therapy used in the treatment of postmenopausal breast cancer. It has a unique mechanism of action in that it causes the degradation of estrogen receptor and therefore has been labeled a selective estrogen receptor downregulator. Unlike the selective estrogen receptor modulator tamoxifen, it has no agonistic properties and is therefore a pure anti-estrogen. Given its low level of bioavailability and presystemic metabolism, it has been formulated as an intramuscular injection. A number of dosing regimens have been utilized – these include a dose of 250 mg monthly (‘approved dose’), an initial 500 mg followed by 250 mg on days 14 and 28, and thereafter 250 mg every 28 days (‘loading dose’), or 500 mg on days 0, 14 and 28, and thereafter every 28 days (‘high dose’). This article will review its unique mode of action and preclinical data, as well as clinical data for different dosing regimens and data for its combination with aromatase inhibitors. Fulvestrant is a well-tolerated drug and its toxicities will also be reviewed. The optimal position of fulvestrant in sequential endocrine therapy has yet to be defined.

Role of Fulvestrant in Sequential Hormonal Therapy for Advanced, Hormone Receptor—Positive Breast Cancer in Postmenopausal Women

The introduction of antiendocrine agents with differing mechanisms of action now mandates the design of rational sequential hormonal regimens for breast cancer. The aromatase inhibitors (AIs), including the nonsteroidal compounds anastrozole and letrozole and the steroidal compound exemestane, are important alternatives or adjuncts to the antiestrogen agent tamoxifen in postmenopausal women with hormone receptor—positive breast cancer in the first-line management of advanced disease and in the adjuvant treatment of early-stage disease. These and other endocrine agents, including the newer estrogen receptor antagonist fulvestrant and also tamoxifen itself, have not been extensively evaluated within the context of hormonal sequencing. Based on a retrospective analysis of data from 3 phase III trials, patients treated with fulvestrant in the first-or second-line hormonal management of advanced breast cancer may derive further clinical benefit from subsequent treatment with an endocrine agent from another class. The need for prospective investigation of post-AI hormonal therapy is intensifying as a result of the increasing clinical use of the AIs. Sophisticated sequencing regimens designed to exploit different mechanisms of action have the potential to confer greater clinical benefit than the historical approach of selecting the agent with the next highest single-agent clinical activity upon disease progression.

Endocrine treatment options for advanced breast cancer – the role of fulvestrant

For many years, tamoxifen has been the ‘gold standard’ amongst anti-oestrogen therapies for breast cancer. However, the selective aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, have demonstrated advantages over tamoxifen as first-line treatments for advanced disease. Anastrozole is also more effective as an adjuvant treatment in early, operable breast cancer and is being increasingly used in the adjuvant setting. Generally, the selective oestrogen receptor modulators (SERMs), such as toremifene, droloxifene, idoxifene, raloxifene, and arzoxifene, show minimal activity in tamoxifen-resistant disease and show no superiority over tamoxifen as first-line treatments. In addition to these agents, other treatment options for advanced disease include high-dose oestrogens and progestins. Response rates for high-dose oestrogens and tamoxifen are similar, but the use of oestrogens is limited by their toxicity profile. Consequently, there is a need for new endocrine treatment options for breast cancer, particularly for use in disease that is resistant to tamoxifen or AIs. Fulvestrant (‘Faslodex’) is a new type of steroidal oestrogen receptor (ER) antagonist that downregulates cellular levels of the ER and progesterone receptor and has no agonist activity. This paper reviews the key efficacy and tolerability data for fulvestrant in postmenopausal women in the context of other endocrine therapies and explores the potential role of fulvestrant within the sequencing of endocrine therapies for advanced breast cancer.