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An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane
Author(s) -
Buzdar Aman U.,
Robertson John F. R.,
Eiermann Wolfgang,
Nabholtz JeanMarc
Publication year - 2002
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.10908
Subject(s) - exemestane , anastrozole , letrozole , medicine , aromatase inhibitor , aromatase , pharmacokinetics , tamoxifen , pharmacology , tolerability , oncology , breast cancer , adverse effect , cancer
Abstract BACKGROUND The newer generation, nonsteroidal aromatase inhibitors (AIs) anastrozole and letrozole have shown superior efficacy compared with tamoxifen as first‐line treatments and compared with megestrol acetate as second‐line therapy in postmenopausal women with advanced breast carcinoma. In an open‐label, Phase II trial, it was reported that exemestane showed numerical superiority compared with tamoxifen for objective response and clinical benefit. Because these agents ultimately may be administered for periods of up to 5 years in the adjuvant setting, it is of increasing importance to assess their tolerability and pharmacologic profiles. METHODS In the absence of data from direct clinical comparisons, the published literature was reviewed for the clinical pharmacology, pharmacokinetic characteristics, and selectivity profiles of anastrozole, letrozole, and exemestane. RESULTS At clinically administered doses, the plasma half‐lives of anastrozole (1 mg once daily), letrozole (2.5 mg once daily), and exemestane (25 mg once daily) were 41–48 hours, 2–4 days, and 27 hours, respectively. The time to steady‐state plasma levels was 7 days for both anastrozole and exemestane and 60 days for letrozole. Androgenic side effects have been reported only with exemestane. Anastrozole treatment had no impact on plasma lipid levels, whereas both letrozole and exemestane had an unfavorable effect on plasma lipid levels. In indirect comparisons, anastrozole showed the highest degree of selectivity compared with letrozole and exemestane in terms of a lack of effect on adrenosteroidogenesis. CONCLUSIONS All three AIs demonstrated clinical efficacy over preexisting treatments. However, there were differences in terms of pharmacokinetics and effects on lipid levels and adrenosteroidogenesis. The long‐term clinical significance of these differences remains to be elucidated. Cancer 2002;95:2006–16. © 2002 American Cancer Society. DOI 10.1002/cncr.10908