Variation in anastrozole metabolism and pharmacodynamics in women with early breast cancer
Autor: | Randy A. Weintraub, Matthew P. Goetz, Clark V. Williard, Daniel J. Schaid, Richard M. Weinshilboum, Anthony Batzler, Janet E. Olson, James N. Ingle, Aman U. Buzdar, Mark E. Robson, Edith A. Perez, Zeruesenay Desta, David A. Flockhart, Donald W. Northfelt |
---|---|
Rok vydání: | 2010 |
Předmět: |
Adult
Cancer Research medicine.medical_specialty medicine.drug_class Estrone Anastrozole Breast Neoplasms Article Cohort Studies chemistry.chemical_compound Breast cancer Internal medicine Nitriles medicine Humans Testosterone Aromatase Aged Aged 80 and over Aromatase inhibitor biology Dose-Response Relationship Drug business.industry Estrogens Middle Aged Triazoles medicine.disease Antiestrogen Postmenopause Endocrinology Oncology chemistry Receptors Estrogen Estrogen Pharmacodynamics biology.protein Female business medicine.drug |
Zdroj: | Cancer research. 70(8) |
ISSN: | 1538-7445 |
Popis: | Aromatase inhibitors play a prominent role in the management of postmenopausal women with endocrine-sensitive breast cancer, but there is large variability in both efficacy and tolerability. The purpose of our study was to define interindividual variation in anastrozole metabolism and pharmacodynamics among patients treated with the approved daily dose of 1 mg in a standard practice setting as adjuvant therapy for resected early breast cancer. This study was performed in 191 women in whom pretreatment and during anastrozole plasma concentrations of estrone (E1), estradiol (E2), estrone conjugates, androstenedione, and testosterone were determined and correlated with plasma concentrations of anastrozole and anastrozole metabolites. There were large interindividual variations in plasma anastrozole and anastrozole metabolite concentrations, as well as pretreatment and postdrug plasma E1, E2, and E1 conjugate and estrogen precursor (androstenedione and testosterone) concentrations. E1 and E2 concentrations were below the lower limit of quantitation (LLQ) in most patients after anastrozole therapy (83% for both), but those with detectable concentrations had a broad range (1.58–45.2 and 0.635–97.0 pg/mL, respectively). E1 conjugates after anastrozole therapy were above the LLQ in most patients (93%), with wide interpatient variability (3.50–2,990 pg/mL). Two patients seemed to extensively metabolize anastrozole and failed to display substantial decreases in estrogens. Acknowledging the potential factor of variable compliance, our results showed large interindividual variation in anastrozole metabolism and its effect on circulating estrogens in postmenopausal patients. These findings may have implications with regard to efficacy and adverse events and may indicate the need to “individualize” therapy with this drug. Cancer Res; 70(8); 3278–86. ©2010 AACR. |
Databáze: | OpenAIRE |
Externí odkaz: |