Titre du document / Document title

An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane

Auteur(s) / Author(s)

BUZDAR Aman U. ⁽¹⁾ ; ROBERTSON John F. R. ⁽²⁾ ; EIERMANN Wolfgang ⁽³⁾ ; NABHOLTZ Jean-Marc ⁽⁴⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, ROYAUME-UNI
⁽²⁾ Professorial Unit of Surgery, City Hospital, Nottingham, ROYAUME-UNI
⁽³⁾ Frauenklinik vom Roten Kreuz, München, ALLEMAGNE
⁽⁴⁾ Medical Hematology and Oncology, University of California at Los Angeles, Los Angeles, California, ETATS-UNIS

Résumé / Abstract

BACKGROUND. The newer generation, nonsteroidal aromatase inhibitors (Als) 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 Als 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.

Revue / Journal Title

Cancer   ISSN 0008-543X   CODEN CANCAR 

Source / Source

2002, vol. 95, n^o9, pp. 2006-2016 [11 page(s) (article)] (62 ref.)

Langue / Language

Anglais

Editeur / Publisher

Wiley-Liss, New York, NY, ETATS-UNIS  (1948) (Revue)

Mots-clés anglais / English Keywords

Enzyme ; Estrogen synthase ; Mammary gland diseases ; Steroid ; Androstane derivatives ; Non steroid compound ; Triazole derivatives ; Enzyme inhibitor ; Antihormone ; Antiestrogen ; Antineoplastic agent ; Secondary effect ; Exemestane ; Letrozole ; Pharmacokinetics ; Anastrozole ; Pharmacology ; Bibliographic review ; Chemotherapy ; Treatment ; Menopause ; Female ; Human ; Mammary gland ; Malignant tumor ;

Mots-clés français / French Keywords

Enzyme ; Estrogen synthase ; Glande mammaire pathologie ; Stéroïde ; Androstane dérivé ; Composé non stéroïde ; Triazole dérivé ; Inhibiteur enzyme ; Antihormone ; Antioestrogène ; Anticancéreux ; Effet secondaire ; Exémestane ; Létrozole ; Pharmacocinétique ; Anastrozole ; Pharmacologie ; Revue bibliographique ; Chimiothérapie ; Traitement ; Ménopause ; Femelle ; Homme ; Glande mammaire ; Tumeur maligne ;

Mots-clés espagnols / Spanish Keywords

Enzima ; Estrogen synthase ; Glándula mamaria patología ; Esteroide ; Androstano derivado ; Compuesto no esteroide ; Triazol derivado ; Inhibidor enzima ; Antihormona ; Antiestrógeno ; Anticanceroso ; Efecto secundario ; Exemestano ; Letrozol ; Farmacocinética ; Anastrozol ; Farmacología ; Revista bibliográfica ; Quimioterapia ; Tratamiento ; Menopausia ; Hembra ; Hombre ; Glándula mamaria ; Tumor maligno ;

Mots-clés d'auteur / Author Keywords

anastrozole ; aromatase inhibitor ; breast carcinoma ; exemestane ; letrozole ; estrogen ; postmenopausal ;

Localisation / Location

INIST-CNRS, Cote INIST : 2701, 35400010517101.0240