Adjuvant therapy for hormone-positive invasive breast cancer in early stages in postmenopausal women. Extended adjuvant therapy for early-stage invasive breast cancer in postmenopausal women who received standard adjuvant therapy with tamoxifen for 5 years. First-line therapy for hormone-dependent advanced breast cancer in postmenopausal women.
active substance: letrozole;
1 coated tablet contains letrozole 2.5 mg;
excipients: lactose monohydrate, microcrystalline cellulose, corn corn starch; sodium starch (type A); magnesium stearate colloidal silicon dioxide;
coating: hypromellose (E 464), talc (E 553b), macrogol 8000, titanium dioxide (E 171), iron oxide yellow (E172)
Letrovista Dosage form
Basic physical and chemical properties: yellow, round, biconvex film-coated tablets with embossed “L9OO” on one side and “2.5” on the other.
Letrovista Pharmacotherapeutic group
Drugs used for hormone therapy. Hormone antagonists and similar agents. Aromatase inhibitors. Letrozole.
ATX code L02B G04.
Letrozole is a non-steroidal aromatase inhibitor (estrogen biosynthesis inhibitor), an antineoplastic drug.
In cases where the growth of tumor tissue depends on the presence of estrogens, the elimination of the stimulating effect mediated by them is a prerequisite for suppressing tumor growth.
In postmenopausal women, estrogens are formed mainly with the participation of the aromatase enzyme, which converts androgens, which are synthesized in the adrenal glands (primarily androstenedione and testosterone), into estrone (E1) and estradiol (E2). Therefore, with the help of specific inhibition of the aromatase enzyme, it is possible to achieve suppression of estrogen biosynthesis in peripheral tissues and in tumor tissue.
Letrozole inhibits aromatase by competitive binding with a subunit of this enzyme – cytochrome P450 heme, which leads to a decrease in estrogen biosynthesis in all tissues.
In healthy postmenopausal women, a single dose of letrozole, which is 0.1 mg, 0.5 mg and 2.5 mg, reduces serum estrone and estradiol levels (compared to baseline) by 75% and 78%, respectively. The maximum reduction is achieved after 48-78 hours.
In women with advanced postmenopausal breast cancer, daily use of letrozole at a dose of 0.1-5 mg reduces plasma levels of estradiol, estrone and estrone sulfate by 75-95% compared to baseline. When using the drug in a dose of 0.5 mg or more, in many cases, the concentration of estrone and estrone sulfate is below the sensitivity limit of the method used to determine hormones. This indicates that with the help of these doses of the drug, a more pronounced inhibition of estrogen synthesis is achieved. The inhibition of estrogen was maintained throughout treatment in all patients.
Letrozole is a highly specific inhibitor of aromatase activity. Disruption of the synthesis of steroid hormones in the adrenal glands was not found. In postmenopausal patients who were treated with letrozole in a daily dose of 0.1-5 mg, clinically significant changes in the plasma concentration of cortisol, aldosterone, 11-deoxycortisol, 17-hydroxyprogesterone, ACTH (ACTH), and renin activity were not detected … The ACTH stimulation test after 6 and 12 weeks of therapy with letrozole at a daily dose of 0.1 mg 0.25 mg 0.5 mg 1 mg 2.5 mg and 5 mg did not reveal any noticeable decrease in the synthesis of aldosterone or cortisol. Thus, there is no need to prescribe glucocorticoids and mineralocorticoids.
In healthy postmenopausal women, after a single use of letrozole at a dose of 0.1 mg, 0.5 mg and 2.5 mg, no changes in the concentration of androgens (androstenedione and testosterone) in the blood plasma were found. In postmenopausal patients who received letrozole in a daily dose of 0.1-5 mg, no changes in the level of androstenedione in the blood plasma were also observed. All this indicates that the blockade of estrogen biosynthesis does not lead to the accumulation of androgens, which are estrogen precursors. In patients treated with letrozole, there were no changes in the concentration of luteinizing hormone (LH) and folliculo hormone (FH) in the blood plasma, and there were no changes in the function of the thyroid gland, which was assessed by the levels of thyroid stimulating hormone (TSH), tritodothyronine (T3) and thyroxine (T4).