Dowsett M, Tobias J S, Howell A, Blackman G M, Welch H, King N, Ponzone R, von Euler M, Baum M
Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.
Br J Cancer. 1999 Jan;79(2):311-5. doi: 10.1038/sj.bjc.6690050.
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.
34名绝经后早期乳腺癌女性患者参与了一项随机、双盲、平行组、多中心试验，这些患者接受过每日一次20毫克他莫昔芬辅助治疗至少10周。该试验的主要目的是确定阿那曲唑对他莫昔芬药代动力学的影响，次要目的是评估两种药物联合使用时的耐受性，以及他莫昔芬是否对阿那曲唑抑制雌二醇有任何影响。患者被随机分为两组，双盲状态下，一组每日一次接受1毫克阿那曲唑（16例患者），另一组接受匹配的安慰剂（18例患者），持续28天。试验期间，阿那曲唑组和安慰剂组的血清他莫昔芬浓度未观察到显著差异（P = 0.919）。在他莫昔芬存在的情况下，与安慰剂组相比，联合使用阿那曲唑的患者血清雌二醇浓度显著降低（P < 0.0001），证实阿那曲唑在他莫昔芬存在时仍是有效的雌二醇抑制剂。他莫昔芬和阿那曲唑联合使用耐受性良好，阿那曲唑组和安慰剂组报告的副作用差异很小。总之，本研究结果证实，对于绝经后早期乳腺癌女性患者，联合使用阿那曲唑和他莫昔芬时，阿那曲唑不影响他莫昔芬的药代动力学。此外，阿那曲唑对雌二醇的抑制作用似乎不受他莫昔芬影响。
