The effect of anastrozole on the pharmacokinetics of tamoxifen in post-menopausal women with early breast cancer

Abstract

Summary Thirty-four post-menopausal women with early breast cancer who had received 20 mg tamoxifen once daily as adjuvant therapy for at least 10 weeks participated in a randomized, double-blind, parallel-group, multicentre trial. The primary aim of the trial was to determine the effect of anastrozole upon tamoxifen pharmacokinetics, with secondary aims of assessing the tolerability of the two drugs in combination and whether or not tamoxifen had any effect upon the oestradiol suppression seen with anastrozole. Patients were randomized to receive either 1 mg anastrozole (16 patients) or matching placebo (18 patients) once daily on a double-blind basis for 28 days. No significant difference (P = 0.919) was observed in serum tamoxifen concentrations between the anastrozole and placebo groups during the trial. The serum concentration of oestradiol was significantly suppressed (P < 0.0001) in patients co-administered anastrozole compared with placebo in the presence of tamoxifen, confirming that anastrozole remained an effective suppressant of oestradiol in the presence of tamoxifen. The combination of tamoxifen and anastrozole was well tolerated, with very little difference in side-effects reported between anastrozole and placebo. In conclusion, the results of this study confirm that anastrozole does not affect the pharmacokinetics of tamoxifen when the two drugs are given in combination to post-menopausal women with early breast cancer. In addition, the oestradiol suppressant effects of anastrozole appear unaffected by tamoxifen.

Drug and hormone interactions of aromatase inhibitors.

“…This was stressed by the study of Lien et al (1990), who demonstrated that combination with AG led to decreases in tamoxifen concentrations of about 70%. We have now performed an analogous study with anastrozole, and found that this inhibitor does not lead to decreased tamoxifen concentrations (Dowsett et al 1999b). In this issue of Endocrine-Related Cancer, Ingle et al (1999) also report that letrozole has no impact on tamoxifen concentrations.…”

Role of Testosterone/Estradiol Ratio in Predicting the Efficacy of Tamoxifen Citrate Treatment in Idiopathic Oligoasthenoteratozoospermic Men

“…It causes a decrease in E2 levels of up to 80% and an increase in gonadotropin and testosterone concentrations [14,23] . Anastrozole does not affect the TAM concentrations [24] .…”

Randomized Biomarker Trial of Anastrozole or Low-Dose Tamoxifen or Their Combination in Subjects with Breast Intraepithelial Neoplasia

“…In the Anastrozole, Tamoxifen Alone or in Combination study, a phase III adjuvant trial with three arms (1 mg anastrozole, 20 mg tamoxifen, and their combination), anastrozole significantly prolonged disease-free survival versus tamoxifen. Moreover, the combination of anastrozole and tamoxifen at the dose of 20 mg/d was inferior to anastrozole alone and slightly, albeit not significantly, worse than tamoxifen alone in terms of disease-free survival, thus leading to the early discontinuation of the combination arm (1,7,8). Different explanations have been advocated, including a documented adverse pharmacokinetic interaction leading to low anastrozole concentrations, although estradiol suppression was similar between anastrozole and combination arms (9) and a predominant estrogenic activity of tamoxifen under anastrozole-induced estrogen-deprived milieu (1).…”