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- Title
Two Decades with the Non-Steroidal Aromatase Inhibitors Letrozole and Anastrozole: Which One is to Prefer?
- Authors
Geisler, Jürgen; Doughty, Julie; Mouridsen, Henning
- Abstract
The two third-generation, non-steroidal aromatase inhibitors (AIs) anastrozole (Arimidex®) and letrozole (Femara®) are currently established as standard therapy in both early and advanced, hormone-sensitive breast cancer in postmenopausal women. While both drugs are highly potent AIs with a similar basic chemical structure (triazoles), results not only from basic endocrine studies but also from clinical trials suggest differences that may be of importance for the patients treated with these compounds. It is the intention of the present overview to summarize the available data and to give the clinicians the necessary information to make the right choice for their breast cancer patients. The first evidence for significant differences between anastrozole and letrozole action was generated during a direct head-to-head comparison of letrozole and anastrozole in postmenopausal breast cancer patients. An intra-patient cross-over study clearly indicated that letrozole is the more effective drug compared to anastrozole concerning "total body aromatase inhibition" and plasma estrogen suppression when administered in the established doses. Recently published studies have suggested that these findings are translated into a better suppression of tumor estrogen levels during letrozole therapy as well. The present overview compares the results of clinical trials using both anastrozole and letrozole in different phases of the breast cancer disease. Briefly, phase-III trials comparing the AIs with tamoxifen not only in early breast cancer but also in the metastatic situation show superior results for the drug that had shown better results in the basic, endocrine studies: letrozole. Finally, the impact of anastrozole and letrozole on distant metastasis, a crucial step in breast cancer progression, is especially emphasized and compared. Again, the results from major clinical trials suggest letrozole to delay the onset of distant metastasis more effectively than anastrozole, potentially explaining the survival benefit seen in the BIG1-98 trial for letrozole and the lack thereof in the ATAC trial for anastrozole. Based on all available information at this time, the overview concludes that the basic differences in pharmacology and endocrinology favoring letrozole are translated into a better clinical efficacy. In addition, according to indirect evidence, adverse events with the two agents seem to be quantitavely and qualitatively similar. In conclusion, letrozole seems to be the preferable drug when compared to anastrozole at present. In some countries, the national guidelines have already been changed accordingly. With further pivotal studies like the FACE-trial ongoing, the subject of this review will remain of high interest in all-day practice in the years to come.
- Subjects
AROMATASE inhibitors; ANASTROZOLE; BREAST cancer; POSTMENOPAUSE; CATECHOL estrogens; SEX hormones
- Publication
European Journal of Clinical & Medical Oncology, 2010, Vol 2, Issue 4, p1
- ISSN
1759-8958
- Publication type
Article