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From Clinical Pharmacology:
From ClinPharm:
Clinical Indication for both: ER positive Breast Cancer.
The difference between these two drugs is like the difference between Nexium and Prevacid. They both prevent acid reflux, the drugs are essentially identical for all practical purposes.
NFG
CLINPharm said:Description: Letrozole is a non-steroidal oral aromatase inhibitor. Unlike aminoglutethimide, an early aromatase inhibitor, letrozole does not inhibit adrenal steroid synthesis. Patients taking letrozole, therefore, do not require glucocorticoid or mineralocorticoid replacement therapy. Letrozole appears to be more effective and better tolerated than megestrol. Final FDA approval was granted July 25, 1997. In January 2001, letrozole was FDA-approved for the first-line treatment of locally advanced or metastatic breast cancer. In October 2004, the FDA granted accelerated approval of letrozole for the extended adjuvant treatment of early breast cancer in postmenopausal women who have received 5 years of adjuvant tamoxifen therapy. Approval was based on the first interim analysis of disease-free survival. Assessment of both safety and overall survival is limited because the study was terminated early due to positive results in the treatment arm. On December 28, 2005, the FDA approved letrozole for the initial adjuvant treatment of hormone receptor positive early breast cancer in postmenopausal women. The approval is based on the interim results of the Breast International Group (BIG) 1—98 study, which enrolled > 8000 patients, comparing 4 study arms: letrozole for 5 years, tamoxifen for 5 years, letrozole for 2 years followed by tamoxifen (total 5 years of therapy), or tamoxifen for 2 years followed by letrozole (total 5 years of therapy). After a median follow-up of 25.8 months, letrozole, as compared to tamoxifen, significantly reduced the risk of recurrent disease (HR 0.81, 95% CI 0.70—0.93, P=0.003). The risk of distant recurrence was also significantly reduced with letrozole (HR 0.73, 95% CI 0.60—0.88, P=0.001). Women in the tamoxifen group experienced more thromboembolic events, endometrial cancer, and vaginal bleeding and women in the letrozole group experienced more bone fractures, cardiac events (ischemic cardiac disease and cardiac failure), and hypercholesterolemia; the overall incidence of life-threatening events was similar between the 2 groups. The majority of the data from this interim analysis reflects data from patients that have received only letrozole or only tamoxifen for approximately 2 years. Further analyses will address the safety and efficacy of continuous letrozole or tamoxifen for 5 years or switching to the alternate endocrine therapy after 2 years.
Mechanism of Action: Letrozole inhibits aromatase, the enzyme that catalyzes the final step in estrogen production. Letrozole competitively binds to the heme of the cytochrome P450 subunit of aromatase. The formation of adrenal corticosteroids, aldosterone, or thyroid hormones is not affected by letrozole; only serum estradiol concentrations are affected by letrozole. In postmenopausal women, the principal source of circulating estrogens is from the conversion of adrenal and ovarian androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) by aromatase in peripheral tissues. Inhibition of aromatase may result in a more complete estrogen block than surgical ablation. Extraglandular sites are more amenable to aromatase inhibition by letrozole than are premenopausal ovaries. Inhibiting the biosynthesis of estrogens is one way to deprive the tumor of estrogens and to restrict tumor growth. Letrozole can reduce circulating estrogen concentrations by 75—95% from the baseline within 2—3 days. Serum lutenizing hormone (LH) or follicle-stimulating hormone (FSH) levels are not affected by letrozole. Aromatase inhibitors might also inhibit estrogen production at the tumor cell. However, tumor production of estradiol may be insignificant because aromatase activity appears to be low.
From ClinPharm:
CLINPharm said:Description: Anastrozole is a nonsteroidal aromatase inhibitor. Anastrozole is highly potent and specific for aromatase, and represents the fourth generation of aromatase inhibitors. Anastrozole significantly suppresses serum estradiol levels, and it offers an alternative to tamoxifen in postmenopausal women with breast cancer. Unlike aminoglutethimide, an early aromatase inhibitor, anastrozole does not inhibit adrenal steroid synthesis. Patients taking anastrozole, therefore, do not require glucocorticoid or mineralocorticoid replacement therapy. Anastrozole causes less weight gain than megestrol and may offer a survival advantage over megestrol in women with advanced breast cancer. Anastrozole was initially FDA-approved for the treatment of advanced breast cancer in postmenopausal women whose disease has progressed during tamoxifen therapy in December 1995. In September 2000, the FDA approved anastrozole for the first-line treatment of postmenopausal women with advanced or metastatic breast cancer. Anastrozole was approved for the adjuvant treatment of early breast cancer in postmenopausal women with hormone receptor-positive disease in September 2002. Accelerated FDA-approval for this indication was based on the preliminary results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial. After a median 33 months of follow-up, postmenopausal women with estrogen-receptor positive tumors treated with anastrozole had statistically significant improvement in disease-free survival of 89.4% at three years compared to 87.4% in the tamoxifen or combination groups. However, there is controversy whether or not this preliminary difference will be clinically significant at the end of 5 years or if these results warrant a change in the current standard of care for this population. In September 2005, anastrozole received full FDA approval for the adjuvant treatment of early breast cancer in postmenopausal women with advanced or metastatic breast cancer. Five-year data from the ATAC trial confirm that anastrozole reduces the risk of breast cancer recurrence when compared to tamoxifen in all patients regardless of estrogen-receptor status (hazards ratio 0.87, 95% confidence interval 0.78—0.97, p=0.01) and in those patients with estrogen-receptor positive breast cancer (hazards ratio 0.83, 95% confidence interval 0.73—0.94, p=0.005). In addition, the time to breast cancer recurrence favored anastrozole. Patients receiving anastrozole experienced fewer adverse events than those receiving tamoxifen. The investigators concluded that anastrozole should be considered as the preferred first-line treatment in this population.
Mechanism of Action: Anastrozole inhibits aromatase, the enzyme that catalyzes the final step in estrogen production. Anastrozole is an oral, competitive, non-steroidal inhibitor of aromatase and is less likely to exhibit agonist or antagonist steroidal properties. The formation of adrenal corticosteroids or aldosterone is not affected by anastrozole; only serum estradiol concentrations are affected by anastrozole. In postmenopausal women, the principal source of circulating estrogens is from the conversion of adrenal and ovarian androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) by aromatase in peripheral tissues. Inhibition of aromatase may result in a more complete estrogen block than surgical ablation. Extraglandular sites are more amenable to aromatase inhibition by anastrozole than are premenopausal ovaries. Inhibiting the biosynthesis of estrogens is one way to deprive the tumor of estrogens and to restrict tumor growth. Estradiol plasma concentrations decrease about 80% from the baseline with continued dosing of anastrozole. Aromatase inhibitors might also inhibit estrogen production at the tumor cell. However, tumor production of estradiol may be insignificant because aromatase activity appears to be low. Anastrozole has little or no effect on CNS, autonomic, or neuromuscular function.
Clinical Indication for both: ER positive Breast Cancer.
The difference between these two drugs is like the difference between Nexium and Prevacid. They both prevent acid reflux, the drugs are essentially identical for all practical purposes.
NFG
