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What is Letrozole?

Feb 10，2020

Letrozole (Femara®) is a nonsteroidal, third-generation aromatase inhibitor administered orally once daily, which has shown efficacy in the treatment of postmenopausal women with early-stage or advanced, hormone-sensitive breast cancer.[1]

Letrozole binds competitively to the heme of cytochrome P450 (CYP) subunit of the aromatase enzyme and its activity is highly specific. In postmenopausal women with breast cancer, letrozole inhibited whole body aromatisation and reduced in-situ aromatisation in breast tumours. The drug had no significant effect on the synthesis of adrenal corticoids, aldosterone or thyroid hormone and did not alter levels of a range of other hormones. No clinically significant effects on blood pressure, pulse, ECG or haematological or biochemical parameters were reported in association with letrozole. Disease flare has not been reported with letrozole. [2]

Absorption of oral letrozole is rapid and complete and steady state is achieved in 2–6 weeks with administration of letrozole 2.5mg once daily. The major route of elimination of letrozole is via metabolism to a pharmacologically inactive carbinol metabolite. The cytochrome P450 (CYP) 3A4 and CYP2A6 isozymes metabolize letrozole to a pharmacologically inactive carbinol metabolite. Renal excretion of a glucuronide conjugate of the carbinol metabolite of letrozole represents the major route of drug clearance. [3]

In addition, both adjuvant and extended adjuvant therapy with letrozole were cost effective in postmenopausal women with early breast cancer from the perspective of US, Canadian and UK healthcare systems. Incremental cost-effectiveness ratios were all below generally accepted cost effectiveness thresholds. [4]

In conclusion, letrozole is an effective and well tolerated treatment for postmenopausal women with early-stage or advanced hormone-responsive breast cancer. Pharmacoeconomic analyses from UK and North American perspectives support the use of letrozole in hormone-responsive early-stage breast cancer in both the adjuvant and extended adjuvant settings. In addition, other modelled analyses conducted in a variety of healthcare systems across different countries consistently suggest that letrozole is cost effective in advanced treatment settings.

References

1.Dragamestianos C, Messini CI, Antonakis PT, Zacharouli K, Kostopoulou E, Makrigiannakis A, Georgoulias P, Anifandis G, Dafopoulos K, Garas A, Daponte A, Messinis IE. The effect of metformin on the endometrium of women with polycystic ovary syndrome[J]. Gynecol Obstet Investig. 2018, 26:1–10.

2.Abu Hashim H. Twenty years of ovulation induction with metformin for PCOS; what is the best available evidence? [J] Reprod BioMed Online. 2016, 32:44–3.

3.Liu W, Dong S, Li Y, Shi L, Zhou W, Liu Y, Liu J, Ji Y. Randomized controlled trial comparing letrozole with laparoscopic ovarian drilling in women with clomiphene citrate-resistant polycystic ovary syndrome[J]. Exp Ther Med. 2015, 10:1297–302.

Franik S, Eltrop SM, Kremer JA, Kiesel L, Farquhar C. Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome[J]. Cochrane Database Syst Rev. 2018, 24(5):CD010287