Fulvestrant (Faslodex®, AstraZeneca) was approved by the FDA for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Fulvestrant is an estrogen receptor (ER) antagonist without known agonist activity.

Fulvestrant binds to the estrogen receptor in a competitive manner with affinity comparable to that of estradiol. Many breast cancers contain estrogen receptors, and the growth of these tumors can be stimulated by estrogen. Fulvestrant down-regulates and degrades the estrogen receptor protein and the receptor in human breast cancer cells.

In a clinical study of postmenopausal women with primary breast cancer treated with single doses of fulvestrant 15 to 22 days before surgery, increasing the dose demonstrated evidence of increasing down-regulation of estrogen receptors. This result was associated with a dose-related decrease in the expression of the progesterone receptor, an estrogen-regulated protein. These effects on the estrogen receptor pathway were also associated with a decrease in the Ki67 labeling index, a marker of cell proliferation.

Intramuscular fulvestrant was compared with the standard therapy for metastatic breast cancer—oral (AstraZeneca), an aromatase inhibitor—in two randomized, controlled clinical trials (a North American double-blinded study and a European open-label study) in postmenopausal women with locally advanced or metastatic breast cancer. In all patients, the cancer had progressed after previous therapy with an antiestrogen or progestin for breast cancer in the adjuvant or advanced disease setting. A total of 851 patients were enrolled, with 428 randomly assigned to receive fulvestrant 250 mg monthly by intramuscular injection and 423 patients randomly assigned to receive anastrazole 1 mg daily. Response rates of 17% and 20% were reported in the fulvestrant treatment arms in the North American and European trials, respectively. These rates were similar to the response rates of 17% and 15% reported in the anastrozole treatment arms. There were no significant differences (P > .05) in time to progression or survival between the two arms in either trial.

The safety profile of fulvestrant was similar to that of anastrazole. Fulvestrant appears to be as effective as anastrazole. The most commonly reported adverse events were of mild to moderate severity, including nausea, vomiting, constipation, diarrhea and abdominal pain, headache, back pain, vasodilation (hot flashes), and pharyngitis. Mild reactions at the injection site were reported in 7% and 27% of patients On 1% and 5% of treatments) who had been given single fulvestrant injections of 5 ml and 2 x 2.5 ml, respectively.

Fulvestrant should not be used in patients with bleeding diatheses or thrombocytopenia or in patients who are taking anticoagulants. Other adverse events that were reported as drug-related and that were observed infrequently (<1%) included throm-boembolic phenomena, myalgia, vertigo, and leukopenia.

Women of childbearing age should be advised not to become pregnant while receiving fulvestrant therapy. No studies of ful-vestrant in pregnant women have been conducted. If fulvestrant is used during pregnancy or if a woman becomes pregnant while receiving fulvestrant, she should be apprised of the potential hazard to the fetus and the potential risk of the loss of the pregnancy.

The recommended daily dose of fulvestrant is 250 mg at one-month intervals, slowly administered into the buttock either as a single 5-ml injection or as two concurrent 2.5-ml injections.


Leuprolide acetate as an injectable suspension (Eligard® 22.5 mg, Atrix Laboratories) is a new proprietary product for the palliative treatment of advanced prostate cancer. An innovative drug-delivery system, Atrigel® (Atrix Laboratories), is used to administer leuprolide acetate over a three-month period. The formulation joins a previously approved leuprolide, a 7.5-mg sustained-release product that is administered once a month.

The American Cancer Society estimates that approximately 189,000 new cases of prostate cancer will be diagnosed in the U.S. in 2002 and approximately 30,200 men will die of the disease. Ac­cording to the National Cancer Institute, most patients with advanced prostate cancer receive luteinizing hormone-releasing hormone (LHRH) therapy during the course of treatment. For men with advanced prostate cancer, the standard treatment regimen often includes starting with one month of LHRH therapy, then switching to a longer-release product if there is a therapeutic response.

Leuprolide acetate is a synthetic nonapeptide analogue of naturally occurring gonadotropin-releasing hormone (GnRH or LHRH) that, when given continuously, inhibits pituitary gonadotropin secretion and suppresses testicular and ovarian steroidogenesis. This effect is reversible upon discontinuation of drug therapy. The analogue possesses greater potency than the natural hormone does.

The administration of 22.5 mg of leuprolide acetate results in an initial increase in circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to a transient increase in levels of the gonadal steroids (testosterone and dihydrotestos-terone in men and estrone and estradiol in premenopausal women). Although patients may experience worsening of symptoms or onset of new signs and symptoms during the first few weeks, continuous administration of leuprolide acetate results in decreased LH and FSH levels. In men, testosterone is reduced to below the castrate threshold (50 ng/dl). These decreases occur within two to four weeks after the initiation of treatment. Long-term studies have shown that continuation of therapy with leuprolide acetate maintains testosterone concentrations below the castrate level for up to seven years and suppresses tumor growth in patients with hormone-responsive prostate cancer. canadian pharmacy cialis

The adverse effects noted during clinical trials with leuprolide after 6 months included mild, transient burning or stinging; mild brief pain in 3.5% of study injections; mild erythema; mild bruising; and mild pruritus. No patient discontinued treatment as a result of adverse events.

The liquid leuprolide products are injected subcutaneously with a small-gauge needle, forming a solid implant in the body. The implant slowly releases leuprolide acetate as the implant is bioabsorbed. The new formulation is administered subcutaneously every three months.

Leuprolide acetate for injection, 22.5 mg, is prefilled and is supplied in two separate sterile syringes whose contents are mixed prior to administration. The two syringes are joined, and the single-dose product is mixed until it is homogenous; it is then injected. One of the two syringes contains the biodegradable, non-gelatin polymeric delivery system.