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At least 19 recordsLinked to original sources
PubMed2002

Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment.

PURPOSE: To compare the efficacy and tolerability of fulvestrant (formerly ICI 182,780) and anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. PATIENTS AND METHODS: Patients (n = 451) with advanced breast cancer were randomized to receive fulvestrant 250 mg as a once-monthly (one x 5 mL) intramuscular injection or an oral dose of anastrozole 1 mg in this open, parallel-group, multicenter trial. The primary end point was time to progression (TTP). Secondary end points included objective response (OR) rates, defined as complete response (CR) or partial response (PR), duration of response (DOR), and tolerability. RESULTS: Patients were followed for a median period of 14.4 months. In terms of TTP, fulvestrant was as effective as anastrozole (hazard ratio, 0.98; confidence interval [CI], 0.80 to 1.21; P =.84). Median TTP was 5.5 months for fulvestrant and 5.1 months for anastrozole. OR rates showed a numerical advantage for fulvestrant (20.7%) over anastrozole (15.7%) (odds ratio, 1.38; CI, 0.84 to 2.29; P =.20). Clinical benefit rates (CR + PR + stable disease > or = 24 weeks) were 44.6% for fulvestrant and 45.0% for anastrozole. Median DOR was 14.3 months for fulvestrant and 14.0 months for anastrozole. Both treatments were well tolerated, with 3.2% and 1.3% of fulvestrant- and anastrozole-treated patients, respectively, withdrawn from treatment because of an adverse event. CONCLUSION: Fulvestrant was as effective as anastrozole. These data confirm that fulvestrant is an additional, effective, and well-tolerated treatment for advanced breast cancer in postmenopausal women whose disease progressed on prior endocrine therapy.

Adult↗
PubMed2002

Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial.

PURPOSE: To compare the efficacy and tolerability of fulvestrant (formerly ICI 182,780) with anastrozole in the treatment of advanced breast cancer in patients whose disease progresses on prior endocrine treatment. PATIENTS AND METHODS: In this double-blind, double-dummy, parallel-group study, postmenopausal patients were randomized to receive either an intramuscular injection of fulvestrant 250 mg once monthly or a daily oral dose of anastrozole 1 mg. The primary end point was time to progression (TTP). Secondary end points included objective response (OR) rate, duration of response (DOR), and tolerability. RESULTS: Patients (n = 400) were followed for a median period of 16.8 months. Fulvestrant was as effective as anastrozole in terms of TTP (hazard ratio, 0.92; 95.14% confidence interval [CI], 0.74 to 1.14; P =.43); median TTP was 5.4 months with fulvestrant and 3.4 months with anastrozole. OR rates were 17.5% with both treatments. Clinical benefit rates (complete response + partial response + stable disease > or = 24 weeks) were 42.2% for fulvestrant and 36.1% for anastrozole (95% CI, -4.00% to 16.41%; P =.26). In responding patients, median DOR (from randomization to progression) was 19.0 months for fulvestrant and 10.8 months for anastrozole. Using all patients, DOR was significantly greater for fulvestrant compared with anastrozole; the ratio of average response durations was 1.35 (95% CI, 1.10 to 1.67; P < 0.01). Both treatments were well tolerated. CONCLUSION: Fulvestrant was at least as effective as anastrozole, with efficacy end points slightly favoring fulvestrant. Fulvestrant represents an additional treatment option for postmenopausal women with advanced breast cancer whose disease progresses on tamoxifen therapy.

Adult↗
PubMed2002

The oncology nurse's role in educating patients on endocrine therapy for metastatic breast cancer--focus on fulvestrant.

Fulvestrant, an estrogen receptor downregulator, is an effective and a safe endocrine option for postmenopausal women with advanced breast cancer who progress or develop recurrent disease on prior endocrine therapy. The recommended dose is 250 mg given as a single 5-mL or 2 concurrent 2.5-mL monthly intramuscular injections. Common adverse events associated with fulvestrant are hot flashes, nausea, and mild injection site reactions. Applying warm or cold compresses to the injection site can minimize injection site reactions. In randomized double-blind clinical trials, the frequency of injection site reactions for fulvestrant are no different from the comparator (anastrozole) arm. Overall, fulvestrant has a safety profile similar to aromatase inhibitors. Advantages of this agent are its effectiveness in tamoxifen-resistant tumors and the lack of agonistic property, creating a favorable side-effect profile. One limitation is that there is no evidence regarding the safety and effectiveness of fulvestrant in premenopausal women. Among endocrine therapies used to treat breast cancer, fulvestrant is unique not only in its mechanism of action but also in its mode of administration. With oral therapies, the patient fills the prescription in a pharmacy and takes the medication home. In contrast, with monthly fulvestrant intramuscular injection, the patient will have increased contact with the nurse. The increased interaction between the patient and the nurse will affect the role of nurses providing patient education and monitoring.

Administration, Oral↗
PubMed2001

Fulvestrant.

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.

Antineoplastic Agents, Hormonal↗
PubMed2002

Fulvestrant: a review of its development, pre-clinical and clinical data.

Hormone therapy is the most important systemic treatment of hormone receptor-positive breast cancer at all stages. Selective oestrogen receptor modulators (SERMs), such as tamoxifen, the mainstay of hormone receptor positive breast cancer manipulation for many years, are limited by their agonist actions. Oestrogen-like activity of these drugs may stimulate cancer growth such as in the endometrium and is a mechanism of resistance in breast cancer. Fulvestrant, the first of a new class of drugs, an oestrogen receptor down regulator, may have advantages over tamoxifen in the treatment of oestrogen-dependent disease. The pre-clinical development and early clinical data of fulvestrant are reviewed. Fulvestrant was as effective as the aromatase inhibitor anastrazole in second-line advanced breast cancer. The phase III trial of fulvestrant versus tamoxifen, as first-line treatment for metastatic breast cancer, has completed accrual and is maturing. Fulvestrant has useful activity against breast cancer as well as a favourable side-effect profile and is likely to represent a useful addition to the fight against hormone dependent breast cancer. Its place will be better defined by ongoing clinical trials.

Animals↗
PubMed2002

Fulvestrant.

Fulvestrant, a novel oestrogen receptor (ER) downregulator, is a pure anti-oestrogen which completely blocks the trophic actions of oestrogens without exerting any partial agonist effects. It reduces expression of oestrogen receptor, progesterone receptor and proliferative and cell turnover indices. The drug is well-tolerated with minimal systemic side effects. Large randomised trials have demonstrated similar efficacy to anastrozole in the treatment of postmenopausal advanced breast cancer. While results of a Phase III trial comparing fulvestrant with tamoxifen as first-line endocrine therapy for postmenopausal advanced breast cancer are awaited, future studies on its role in adjuvant and neoadjuvant settings, as well as in premenopausal women are required. With the role of tamoxifen as the gold standard of first-line therapy being challenged by the third generation aromatase inhibitors, direct comparison of the latter with fulvestrant in the first-line setting may also be worthwhile.

Animals↗
PubMed2002

Fulvestrant (AstraZeneca).

Fulvestrant (Faslodex) is an estrogen receptor (ER) downregulator under development by AstraZeneca for the potential treatment of breast cancer [172191], [237518], [314472], [349551]. In March 2001, an NDA was filed in the US for the second-line treatment of advanced breast cancer in postmenopausal women who have progressed on prior hormonal therapy [403574], [434825]; in December 2001, AstraZeneca was expecting to launch the compound in the US in thefirst half of 2002 [431887]. In August 2001, late-stage clinical trials were ongoing in Japan for breast cancer [422343]. Fulvestrant also has potential in the treatment of other estrogen-responsive tumors, such as uterine tumors [178081]. By 1997, fulvestrant was in phase II trials for uterine fibroids [272162], and by February 1999, it was reported that phase II trials for endometriosis were ongoing [314472], [336599]. However, no development has been reported for these indications since that time. In October 2001, Morgan Stanley expected launch in 2002, with estimated sales of $80 million in 2002 rising to $208 million in 2007 [429700]. Analysts at Lehman Brothers predicted in December 2001, that the product has a 90% chance of making it to market in 2002, with peak sales potential in this year of $800 million [434768].

Animals↗
PubMedDate not supplied

Fulvestrant, an estrogen receptor downregulator, reduces cell turnover index more effectively than tamoxifen.

BACKGROUND: This study was performed to determine whether drug action on breast tumours could also be analysed using a cell turnover index (CTI), a composite measurement of both proliferation and apoptosis. MATERIALS AND METHODS: Data were obtained from a randomized, placebo-controlled trial comparing three single doses (50, 125 and 250 mg) of intramuscular fulvestrant (Faslodex, previously known as ICI 182,780) with oral tamoxifen 20 mg/day for 14-21 days in women with early, operable, ER-positive breast cancer. CTI was calculated as the ratio of the proliferation index to the apoptotic index. RESULTS: Fulvestrant 250 mg significantly reduced CTI compared with both placebo (p = 0.0003) and tamoxifen (p = 0.026). The effect on CTI with tamoxifen was not significantly different from that with placebo. CONCLUSION: This study suggests that CTI may be a useful indicator of drug action on breast tumour growth. A significant reduction in growth was found with fulvestrant 250 mg compared with tamoxifen.

Antineoplastic Agents↗
PubMed2002

Fulvestrant (Faslodex): current status in the therapy of breast cancer.

Fulvestrant (Faslodex, formerly ICI 182,780) is a potent steroidal antiestrogen that mediates its effects by estrogen receptor downregulation. It appears to act as a pure antiestrogen and exhibits none of the negative side effects associated with the partial agonist activity of tamoxifen. It has been shown to be as effective as the oral aromatase inhibitor anastrozole in postmenopausal women with advanced breast cancer who have progressed on prior endocrine therapy, principally tamoxifen. It therefore provides the clinician with an alternative therapeutic strategy following the development of tamoxifen resistance. Fulvestrant might also have potential as a follow-on therapy after tamoxifen in an adjuvant setting and help alleviate some of the concerns surrounding long-term (up to 5 years) tamoxifen therapy.

Animals↗
PubMed2026

Screening of Estrogenic and Antiestrogenic Effects of Estradiol, Bisphenol A, and Fulvestrant Using 2D and 3D Breast Cancer Cell Systems With a Luciferase Reporter Gene Assay.

Endocrine-disrupting chemicals (EDCs) like bisphenol A (BPA) pose health risks by interfering with hormones. This study develops and utilizes in&#xa0;vitro 2D and 3D cell models to evaluate the estrogenic and antiestrogenic properties of compounds. Human breast cancer cell lines T47D and MCF7, stably transfected with a luciferase reporter gene (ERE-LUC), were first compared in 2D. Due to the significantly higher sensitivity and responsiveness observed in the T47D line during preliminary 2D screenings, this cell line was exclusively selected for the development of the 3D spheroid model. Cells were treated with 17&#x3b2;-estradiol (E2), BPA, and Fulvestrant (FUL) to assess cell viability and luciferase activity. In 2D models, T47D ERE-LUC cells showed higher responsiveness than MCF7 ERE-LUC, which failed to show significant luciferase induction with E2. In the 3D T47D model, cells exhibited significant and robust changes in luciferase activity in response to E2 and BPA, highlighting the enhanced fidelity of 3D cultures in replicating tissue conditions compared to their 2D counterparts. The study highlights the effectiveness of 3D models over 2D in evaluating estrogenic activity. Specifically, the 3D T47D ERE-LUC system serves as a superior, sensitive, and reliable platform for screening EDCs, offering benefits in cost, data speed, and reduced in&#xa0;vivo reliance.

Humans↗
PubMed2001

ICI 182,780 (Fulvestrant)--the first oestrogen receptor down-regulator--current clinical data.

ICI 182,780 (Fulvestrant) is the first in a new class of novel, steroidal, 'pure' antioestrogens--the oestrogen receptor (ER) down-regulators. Its unique mode of action and the absence of partial agonist activity make it a candidate for the treatment of advanced breast cancer in both pre- and postmenopausal women. Tamoxifen has been available for use over the past 25 years. However, its partial agonist activity has been associated with detrimental effects, particularly on the endometrium, and may be associated with the development of tamoxifen resistance. Other antioestrogen agents have previously been unable to demonstrate clinically relevant activity following the development of resistance to tamoxifen. In contrast, the unique mechanism of action of ICI 182,780 results in significant clinical activity in patients failing on tamoxifen therapy. Indeed, phase III clinical trials have demonstrated that ICI 182,780 is at least as effective as the aromatase inhibitor anastrozole in the treatment of postmenopausal patients with advanced disease who have progressed during threatment with prior enocrine therapy. As such, ICI 182,780 will provide a valuable addition to the armamentarium for the treatment of advanced breast cancer.

Antineoplastic Agents↗
PubMed2002

Persistent suppression of hepatic CYP2A1 expression and serum triiodothyronine levels by tamoxifen in intact female rats: dose-response analysis and comparison with 4-hydroxytamoxifen, fulvestrant (ICI 182,780), and 17beta-estradiol-3-benzoate.

Tamoxifen, a nonsteroidal antiestrogen, is used widely in the treatment of breast cancer and is undergoing evaluation as a chemopreventive agent. In this study, we investigated several long-term effects of tamoxifen in intact adult female rats following acute treatment at various dosages. The effects of tamoxifen on somatic growth, growth hormone (GH) levels, thyroid hormone levels, and on hepatic cytochrome P450 (P450) expression were compared with those of fulvestrant (ICI 182,780), 17beta-estradiol-3-benzoate, and 4-hydroxytamoxifen under the same experimental conditions. Each compound was injected s.c. for two consecutive days, and rats were killed 37 days after treatment. Tamoxifen decreased body weight and serum triiodothyronine (T3) levels at dosages ranging from 0.5 to 200 mg/kg. Ovary weight, uterus weight, peak plasma GH concentration, and hepatic CYP2A1 content were decreased 37 days after treatment with tamoxifen at a dosage of 20 mg/kg, but expression of other P450 enzymes was not affected. However, tamoxifen and 4-hydroxytamoxifen could not be detected in plasma by high performance liquid chromatography analysis at this time, which suggests that the effects of tamoxifen were mediated indirectly. 4-Hydroxytamoxifen exhibited effects similar to those of tamoxifen, indicating that this metabolite contributes to the in vivo activity of tamoxifen. Estradiol benzoate decreased CYP2A1 and increased CYP3A hepatic levels, but had no effect on serum T3 concentration. In contrast, treatment with ICI 182,780 had little or no effect on the endpoints measured. In summary, 2-day tamoxifen treatment of intact adult female rats resulted in persistent suppression of somatic growth, serum T3 levels, and hepatic CYP2A1 expression.

Animals↗
PubMed2002

Estrogen receptor downregulators: new antihormonal therapy for advanced breast cancer.

BACKGROUND: Fulvestrant is the first agent in the new class of estrogen receptor (ER) downregulators to be evaluated in clinical studies. The binding of ER downregulators to ERs inhibits the activation functions of the receptors (AF-1 and AF-2). ER downregulators also disrupt the dimerization and nuclear localization of ERs. In contrast to ER downregulators, when selective estrogen receptor modulators (SERMs) bind to ERs, only AF-2 is inhibited; AF-1 remains active. Therefore, with SERMs, AF-1 can still recruit coactivators, which results in a partially inactivated transcription and a reduced rate of tumor cell division. Consistent with its mechanism of action, animal models have shown that fulvestrant demonstrates a longer suppression of tumor growth than does tamoxifen, and it has antitumor activity in tamoxifen-resistant tumors. Two Phase III trials have been conducted comparing fulvestrant (250 mg IM monthly) with anastrozole (1 mg oral tablet daily) in postmenopausal patients with advanced breast cancer progressing after prior endocrine therapy. Objective response in fulvestrant-treated patients in the 2 studies ranged from 17.5% to 20.7% compared with 15.7% to 17.5% for anastrozole-treated patients, and the median duration of response ranged from 14.3 to 19.3 months in the fulvestrant group compared with 10.5 to 14.0 months in the anastrozole group. No statistically significant differences were demonstrated for any of the predefined end points. In both studies, fulvestrant was as well tolerated as anastrozole. OBJECTIVE: This review describes the pharmacology, clinical activity, safety, dosing, and pharmacokinetic profile of fulvestrant. CONCLUSIONS: Based on evidence to date, fulvestrant will likely be an important agent in the treatment of tamoxifen-resistant metastatic breast cancer.

Animals↗
PubMed2002

A new estrogen receptor antagonist--an overview of available data.

Fulvestrant ('Faslodex'), a novel estrogen receptor (ER) antagonist with no known agonist effects that downregulates the ER, is the first in a new class of antiestrogen. Consequently, fulvestrant is not cross-resistant with other endocrine therapies. In previously untreated postmenopausal women, fulvestrant brought about dose-dependent reductions in ER and progesterone receptor (PgR) protein concentrations and produced no demonstrable estrogen agonist effect. Fulvestrant has demonstrated clinical benefit rates of 69% in postmenopausal women with advanced tamoxifen-resistant breast cancer. In two global phase III trials, fulvestrant was shown to be at least as effective as the aromatase inhibitor anastrozole with similar efficacy for time to progression, objective response and clinical benefit in patients progressing on prior endocrine therapy. Fulvestrant was also well tolerated and, similar to anastrozole, maintained a good quality of life. As a once-monthly intramuscular injection, administered during clinic visits, fulvestrant offers patient compliance advantages, making this new hormonal agent a viable therapeutic option for the palliative treatment of postmenopausal women with endocrine-responsive advanced breast cancer.

Antineoplastic Agents, Hormonal↗
PubMed2001

Preliminary experience with pure antiestrogens.

Endocrine therapy plays an important role in the management of all stages of breast cancer, and the development of effective endocrine therapies has focused on modifying the response of hormone-sensitive tumors to estrogen. The most widely used agents are the nonsteroidal antiestrogens or selective estrogen receptor (ER) modulators, the class to which tamoxifen, the standard in terms of antiestrogen therapy, belongs. Tamoxifen is effective in both adjuvant and first-line settings and is now used as prophylactic therapy in high-risk individuals. However, the partial agonist activity of tamoxifen on the uterus, coupled with "tumor flare" and the development of tamoxifen resistance, has limited its therapeutic utility. Attempts to eliminate the partial agonist activity of tamoxifen and increase its potency have led to the development of fulvestrant (Faslodex), the first in a new class of pure antiestrogens, the ER down-regulators. Fulvestrant has a high affinity for the ER compared with tamoxifen but has none of the agonist activities of tamoxifen. This new agent is showing promising clinical activity in the treatment of advanced breast cancer after tamoxifen therapy. Fulvestrant's lack of ER agonist activity may provide a longer duration of response compared with tamoxifen, as it did in a preclinical setting. Fulvestrant has demonstrated that it is at least as effective as the third-generation aromatase inhibitor anastrozole in patients whose disease has relapsed or recurred on prior endocrine therapy and is currently being evaluated in Phase III trials versus tamoxifen for the first-line therapy of advanced breast cancer. Future clinical studies will evaluate fulvestrant in adjuvant and neoadjuvant settings, together with its optimal sequencing in relation to tamoxifen and other endocrine therapies.

Animals↗
PubMed2001

Pure antiestrogens and breast cancer.

Tamoxifen, which is the most commonly used drug for treatment of breast cancer, has both estrogen agonist and antagonist actions. Pure antiestrogens are devoid of any estrogen agonist effects. ICI 182,780 (fulvestrant) (Faslodex) and ICI 164,384 are competitive inhibitors of estrogen by binding to the estrogen receptor (ER). Preclinical and clinical studies show that fulvestrant and ICI 164,384 are more potent than tamoxifen in inhibiting the growth of breast cancer cells. They are devoid of any estrogen-agonist action on the uterus and vagina but lack the beneficial effects of tamoxifen on the bone and serum lipid profile. Fulvestrant is the first pure antiestrogen to complete phase III clinical trials. Such studies have shown that fulvestrant is at least as good as anastrozole in the treatment of post-menopausal women with advanced breast cancer who had relapsed or progressed on prior endocrine therapy. The drug was well tolerated and only minor side-effects were reported. Its potential role in the adjuvant setting will be determined by its adverse effects on bone mass and serum lipids. EM-800 and EM-652 are the most potent pure antiestrogens and EM-652 has the highest affinity of all antiestrogens to ER. They have no stimulatory effects on the uterus or vagina. It seems reasonable to expect that pure antiestrogens will be good alternatives to tamoxifen and aromatase inhibitors in the treatment of breast cancer.

Antineoplastic Agents, Hormonal↗