03-03-2005, 11:12 AM #1
Injectable sustained release anti estrogen
Anyone ever heard or used? First example I was just turned on to was Fastlodex??? Come on scientist, researchers, and pre-knowledgable members.(hooker, big k.l.g, buff87, and way more than I am listing - you say... I absorb)
Last edited by Mesomorphyl; 03-03-2005 at 12:05 PM.
03-03-2005, 11:14 AM #2
03-03-2005, 12:26 PM #3
03-03-2005, 01:01 PM #4
Here is something...
Many breast cancers have estrogen receptors (ER), and the growth of these tumors can be stimulated by estrogen. Fulvestrant is an estrogen receptor antagonist that binds to the estrogen receptor in a competitive manner with affinity comparable to that of estradiol. Fulvestrant downregulates the ER protein in human breast cancer cells. In a clinical study in postmenopausal women with primary breast cancer treated with single doses of FASLODEX 15-22 days prior to surgery, there was evidence of increasing down regulation of ER with increasing dose. This was associated with a dose-related decrease in the expression of the progesterone receptor, an estrogen-regulated protein. These effects on the ER pathway were also associated with a decrease in Ki67 labeling index, a marker of cell proliferation. In vitro studies demonstrated that fulvestrant is a reversible inhibitor of the growth of tamoxifen -resistant, as well as estrogen-sensitive human breast cancer (MCF-7) cell lines. In in vivo tumor studies, fulvestrant delayed the establishment of tumors from xenografts of human breast cancer MCF-7 cells in nude mice. Fulvestrant inhibited the growth of established MCF-7 xenografts and of tamoxifen-resistant breast tumor xenografts. Fulvestrant resistant breast tumor xenografts may also be cross-resistant to tamoxifen. Fulvestrant showed no agonist-type effects in in vivo uterotropic assays in immature or ovariectomized mice and rats. In in vivo studies in immature rats and ovariectomized monkeys, fulvestrant blocked the uterotrophic action of estradiol. In postmenopausal women, the absence of changes in plasma concentrations of FSH and LH in response to fulvestrant treatment (250 mg monthly) suggests no peripheral ********* effects.
Summary Efficacy of FASLODEX was established by comparison to the selective aromatase inhibitor anastrozole in two randomized, controlled clinical trials (one conducted in North America, the other in Europe) in postmenopausal women with locally advanced or metastatic breast cancer. All patients had progressed after previous therapy with an antiestrogen or progestin for breast cancer in the adjuvant or advanced disease setting. The majority of patients in these trials had ER+ and/or PgR+ tumors. Patients who had ER-/PgR- or unknown disease must have shown prior response to endocrine therapy. In both trials, eligible patients with measurable and/or evaluable disease were randomized to receive either FASLODEX 250 mg intramuscularly once a month (28 days + 3 days) or anastrozole 1 mg orally once a day. All patients were assessed monthly for the first three months and every three months thereafter. The North American trial was a double-blind, randomized trial in 400 postmenopausal women. The European trial was an open, randomized trial conducted in 451 patients. Patients on the FASLODEX arm of the North American trial received two separate injections (2 X 2.5 ml), whereas FASLODEX patients received a single injection (1 X 5 ml) in the European trial. In both trials, patients were initially randomized to a 125 mg per month dose as well, but interim analysis showed a very low response rate and low dose groups were dropped. The effectiveness endpoints were response rates (RR), based on the Union Internationale Contre le Cancer (UICC) criteria, and time to progression (TTP). Survival time was also determined. Confidence intervals (95.4%) were calculated for the difference in RR between the FASLODEX and anastrozole groups. The hazard ratio for an unfavorable event, (such as disease progression or death) between FASLODEX and anastrozole groups was also determined. Table 2 provides the demographics and baseline characteristics of the postmenopausal women randomized to FASLODEX 250 mg or anastrozole 1 mg. Results of the trials, after a minimum follow-up duration of 14.6 months, are summarized in Table 3. The effectiveness of FASLODEX 250 mg was determined by comparing RR and TTP results to anastrozole 1 mg, the active control. With respect to response rate, the two studies ruled out (by one-sided 97.7% confidence limit) inferiority of FASLODEX to anastrozole of 6.3% and 1.4%. (See Table) CR = Complete Response; PR = Partial Response; CI = Confidence Interval; FAS = FASLODEX; ANA = anastrozole There are no efficacy data for the use of FASLODEX in premenopausal women with advanced breast cancer (women with functioning ovaries as evidenced by menstruation and/or premenopausal LH, FSH and estradiol levels).
Mechanism of Action FASLODEX (fulvestrant) Injection for intramuscular administration is an estrogen receptor antagonist without known agonist effects. The chemical name is 7-alpha-[9-(4,4,5,5,5-penta fluoropentylsulphinyl) nonyl]estra-1,3,5-(10)- triene-3,17-beta-diol. is C32H47F5O3S Fulvestrant is a white powder with a molecular weight of 606.77. The solution for injection is a clear, colorless to yellow, viscous liquid. Each injection contains as inactive ingredients: Alcohol, USP, Benzyl Alcohol, NF, and Benzyl Benzoate, USP, as co-solvents, and Castor Oil, USP as a co-solvent and release rate modifier. FASLODEX is supplied in sterile single patient pre-filled syringes containing 50-mg/mL fulvestrant either as a single 5 mL or two concurrent 2.5 mL injections to deliver the required monthly dose. FASLODEX is administered as an intramuscular injection of 250 mg once monthly.
03-03-2005, 01:44 PM #5VET Retired
- Join Date
- Dec 2001
I heard it runs over 500 us per ml.
03-03-2005, 01:45 PM #6Originally Posted by big k.l.g
Thanks big k.l.g
03-03-2005, 03:53 PM #7Writer
- Join Date
- Apr 2002
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