Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Jan;79(2):311–315. doi: 10.1038/sj.bjc.6690050

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

M Dowsett 1, J S Tobias 2, A Howell 3, G M Blackman 2, H Welch 1, N King 1, R Ponzone 1, M von Euler 4, M Baum 5
PMCID: PMC2362190  PMID: 9888474

Abstract

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. © 1999 Cancer Research Campaign

Keywords: Arimidex, tamoxifen, aromatase inhibitor, oestrogen, oestradiol, breast cancer

Full Text

The Full Text of this article is available as a PDF (70.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bratherton D. G., Brown C. H., Buchanan R., Hall V., Kingsley Pillers E. M., Wheeler T. K., Williams C. J. A comparison of two doses of tamoxifen (Nolvadex) in postmenopausal women with advanced breast cancer: 10 mg bd versus 20 mg bd. Br J Cancer. 1984 Aug;50(2):199–205. doi: 10.1038/bjc.1984.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buzdar A., Jonat W., Howell A., Jones S. E., Blomqvist C., Vogel C. L., Eiermann W., Wolter J. M., Azab M., Webster A. Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. Arimidex Study Group. J Clin Oncol. 1996 Jul;14(7):2000–2011. doi: 10.1200/JCO.1996.14.7.2000. [DOI] [PubMed] [Google Scholar]
  3. Dowsett M., Goss P. E., Powles T. J., Hutchinson G., Brodie A. M., Jeffcoate S. L., Coombes R. C. Use of the aromatase inhibitor 4-hydroxyandrostenedione in postmenopausal breast cancer: optimization of therapeutic dose and route. Cancer Res. 1987 Apr 1;47(7):1957–1961. [PubMed] [Google Scholar]
  4. Dukes M., Edwards P. N., Large M., Smith I. K., Boyle T. The preclinical pharmacology of "Arimidex" (anastrozole; ZD1033)--a potent, selective aromatase inhibitor. J Steroid Biochem Mol Biol. 1996 Jul;58(4):439–445. doi: 10.1016/0960-0760(96)00064-7. [DOI] [PubMed] [Google Scholar]
  5. Geisler J., King N., Dowsett M., Ottestad L., Lundgren S., Walton P., Kormeset P. O., Lønning P. E. Influence of anastrozole (Arimidex), a selective, non-steroidal aromatase inhibitor, on in vivo aromatisation and plasma oestrogen levels in postmenopausal women with breast cancer. Br J Cancer. 1996 Oct;74(8):1286–1291. doi: 10.1038/bjc.1996.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gelber R. D., Goldhirsch A., Coates A. S. Adjuvant therapy for breast cancer: understanding the overview. International Breast Cancer Study Group. J Clin Oncol. 1993 Mar;11(3):580–585. doi: 10.1200/JCO.1993.11.3.580. [DOI] [PubMed] [Google Scholar]
  7. Howell A., Downey S., Anderson E. New endocrine therapies for breast cancer. Eur J Cancer. 1996 Apr;32A(4):576–588. doi: 10.1016/0959-8049(96)00032-9. [DOI] [PubMed] [Google Scholar]
  8. Howell A., Dowsett M. Recent advances in endocrine therapy of breast cancer. BMJ. 1997 Oct 4;315(7112):863–866. doi: 10.1136/bmj.315.7112.863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ingle J. N., Green S. J., Ahmann D. L., Long H. J., Edmonson J. H., Rubin J., Chang M. N., Creagan E. T. Randomized trial of tamoxifen alone or combined with aminoglutethimide and hydrocortisone in women with metastatic breast cancer. J Clin Oncol. 1986 Jun;4(6):958–964. doi: 10.1200/JCO.1986.4.6.958. [DOI] [PubMed] [Google Scholar]
  10. Jacolot F., Simon I., Dreano Y., Beaune P., Riche C., Berthou F. Identification of the cytochrome P450 IIIA family as the enzymes involved in the N-demethylation of tamoxifen in human liver microsomes. Biochem Pharmacol. 1991 Jun 15;41(12):1911–1919. doi: 10.1016/0006-2952(91)90131-n. [DOI] [PubMed] [Google Scholar]
  11. Johnston S. R., Haynes B. P., Sacks N. P., McKinna J. A., Griggs L. J., Jarman M., Baum M., Smith I. E., Dowsett M. Effect of oestrogen receptor status and time on the intra-tumoural accumulation of tamoxifen and N-desmethyltamoxifen following short-term therapy in human primary breast cancer. Breast Cancer Res Treat. 1993 Dec;28(3):241–250. doi: 10.1007/BF00666585. [DOI] [PubMed] [Google Scholar]
  12. Lien E. A., Anker G., Lønning P. E., Solheim E., Ueland P. M. Decreased serum concentrations of tamoxifen and its metabolites induced by aminoglutethimide. Cancer Res. 1990 Sep 15;50(18):5851–5857. [PubMed] [Google Scholar]
  13. Milsted R., Habeshaw T., Kaye S., Sangster G., Macbeth F., Campbell-Ferguson J., Smith D., Calman K. A randomised trial of tamoxifen versus tamoxifen with aminoglutethimide in post-menopausal women with advanced breast cancer. Cancer Chemother Pharmacol. 1985;14(3):272–273. doi: 10.1007/BF00258132. [DOI] [PubMed] [Google Scholar]
  14. Patterson J. S., Settatree R. S., Adam H. K., Kemp J. V. Serum concentrations of tamoxifen and major metabolite during long-term nolvadex therapy, correlated with clinical response. Eur J Cancer. 1980;Suppl 1:89–92. [PubMed] [Google Scholar]
  15. Plourde P. V., Dyroff M., Dukes M. Arimidex: a potent and selective fourth-generation aromatase inhibitor. Breast Cancer Res Treat. 1994;30(1):103–111. doi: 10.1007/BF00682745. [DOI] [PubMed] [Google Scholar]
  16. Rose C., Kamby C., Mouridsen H. T., Bastholt L., Brincker H., Skovgaard-Poulsen H., Andersen A. P., Loft H., Dombernowsky P., Andersen K. W. Combined endocrine treatment of postmenopausal patients with advanced breast cancer. A randomized trial of tamoxifen vs. tamoxifen plus aminoglutethimide and hydrocortisone. Breast Cancer Res Treat. 1986;7 (Suppl):S45–S50. [PubMed] [Google Scholar]
  17. Yates R. A., Dowsett M., Fisher G. V., Selen A., Wyld P. J. Arimidex (ZD1033): a selective, potent inhibitor of aromatase in postmenopausal female volunteers. Br J Cancer. 1996 Feb;73(4):543–548. doi: 10.1038/bjc.1996.94. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES