Letrozole: An Updated Review of its Use in Postmenopausal Women with Advanced Breast Cancer

Authors: Keating G.M.; Jarvis B.

Source: American Journal of Cancer, Volume 1, Number 5, 2002 , pp. 351-371(21)

Publisher: Adis International

Abstract:

Letrozole is a highly selective nonsteroidal aromatase inhibitor. In postmenopausal women with advanced breast cancer, letrozole inhibits whole body aromatization by >98% and reduces plasma levels of estrone, estradiol and estrone sulfate by 74 to >95%. It also significantly inhibits aromatase activity and significantly reduces endogenous estrogen levels within breast tumors.

Letrozole is superior to tamoxifen in the first-line treatment of postmenopausal women with advanced breast cancer. In a large, well designed trial, letrozole recipients were significantly less likely than tamoxifen recipients to experience disease progression or treatment failure and significantly more likely to experience an objective response or clinical benefit. The survival rate was significantly higher in letrozole than in tamoxifen recipients at 1 and 2 years.

In the second-line treatment of postmenopausal women with advanced breast cancer, letrozole was at least as effective as megestrol and was superior to aminoglutethimide, according to the results of three large, well designed trials. Letrozole 2.5 mg/day recipients were significantly more likely than letrozole 0.5 mg/day recipients or megestrol recipients to achieve an objective response in one trial, while no difference between the three treatment groups was seen in a second study. However, in this study, a significantly lower risk of disease progression and treatment failure was seen in letrozole 0.5 mg/day than in megestrol recipients. In the other trial, letrozole 2.5 mg/day, compared with megestrol, recipients were significantly less likely to experience treatment failure and had significantly longer durations of objective response and clinical benefit. Compared with aminoglutethimide recipients, letrozole recipients were significantly less likely to experience disease progression or treatment failure, and had significantly prolonged survival.

Second-line therapy with letrozole was associated with a significantly higher overall response rate than anastrozole in postmenopausal women with advanced breast cancer.

Letrozole was generally well tolerated in postmenopausal women with advanced breast cancer with adverse events tending to be of mild-to-moderate severity. Letrozole had similar tolerability to tamoxifen in the first-line treatment of advanced breast cancer. In terms of second-line treatment, letrozole appeared to be better tolerated than megestrol, aminoglutethimide or anastrozole.

Conclusion: Letrozole is an effective option in the first- and second-line treatment of postmenopausal women with advanced breast cancer who have hormone receptor-positive disease or disease of unknown receptor status. Letrozole is superior to tamoxifen in the first-line treatment of advanced breast cancer and at least as effective as megestrol, with better tolerability, in the second-line treatment of advanced breast cancer.

Keywords: Adis Drug Evaluations; Advanced breast cancer, treatment; Aminoglutethimide, therapeutic use; Anastrozole, therapeutic use; Antineoplastics, general; Aromatase inhibitors, general; Fadrozole, therapeutic use; Letrozole, general; Megestrol, therapeutic use; Menopause; Pharmacoeconomics; Quality of life

Language: English

Document Type: Drug Evaluation

Affiliations: 1: Adis International Inc., Langhorne, Pennsylvania, USA *

Publication date: 2002-01-01

• In this: publication
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• In this Subject: Oncology
• By this author: Keating G.M. ;  Jarvis B.

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