Abstract
Anastrozole (Arimidex®, 2,-2[5-(1H-1,2,4-triazol-1-ylmethyl)-1,3- phenylene]bis(2-methyl)propiononitrile) is a novel, potent aromatase inhibitor belonging to the triazole class. In vitro and in vivo animal studies have revealed the drug to be a potent inhibitor of the aromatase enzyme with no inhibitory activity versus other enzymes involved in steroid synthesis. The drug is a potent suppressor of plasma estrogens in healthy male and postmenopausal female volunteers as well as postmenopausal breast cancer patients, and anastrozole administered as 1 mg or 10 mg daily has been shown to inhibit in vivo aromatization by 96.7 and 98.1%, respectively. Two large, randomized studies revealed anastrozole to cause objective response rates and stable disease comparable to what was achieved with megestrol acetate but with a lower incidence of side effects. While follow-up results have not revealed any significant difference in time to relapse between the drug regimens, they have revealed an improved survival among patients treated with anastrozole 1 mg compared to megestrol acetate 160 mg daily. Further follow-up is required to finally decide whether there may be a survival benefit also among patients treated with anastrozole 10 mg daily and to evaluate whether the improvement in survival is associated with an improved disease-free survival as would be anticipated.
Similar content being viewed by others
References
Lønning PE, Kvinnsland S: Mechanism of action of aminoglutethimide as endocrine therapy of breast cancer. Drugs 35: 685–710, 1988
MacNeill FA, Jones AL, Jacobs S, Lønning PE, Powels TJ, Dowsett M: The influence of aminoglutethimide and its analogue rogletimide on peripheral aromatisation in breast cancer. Br J Cancer 66: 692–697, 1992
Dowsett M, MacNeill F, Mehta A, Newton C, Haynes B, Jones A, Jarman M, Lønning P, Powles TH, Coombes RC: Endocrine, pharmacokinetic and clinical studies of the aromatase inhibitor 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione (‘pyridoglutethimide’) in postmenopausal breast cancer patients. Br J Cancer 64: 887–894, 1991
Steele RE, Mellor LB, Sawyer WK, Wasvary JM, Browne LJ: In vitro and in vivo studies demonstrating potent and selective estrogen inhibition with the nonsteroidal aromatase inhibitor CGS 16949A. Steroids 50: 147–161, 1987
Dowsett M, Stein RC, Mehta A, Coombes RC: Potency and selectivity of the non-steroidal aromatase inhibitor CGS 16949A in postmenopausal breast cancer patients. Clin Endocrinol 32: 623–634, 1990
Lønning PE, Jacobs S, Jones A, Haynes B, Powles T, Dowsett M: The influence of CGS 16949A on peripheral aromatisation in breast cancer patients. Br J Cancer 63: 789–793, 1991
Dukes M, Edwards PN, Large M, Smith IK, Boyle T: The preclinical pharmacology of ‘arimidex’ (anastrozole; ZD1033)—a potent, selective aromatase inhibitor. J Steroid Biochem Mol Biol 58: 439–445, 1996
Dukes M, Edvards PN, Large M, Frank R, Yates RA, Deberardinis M, Plourde PV: ICI1033, a new, selective, non-steroidal aromatase inhibitor. Proc Am Assoc Cancer Res 33 (Abstr. 1677): 280, 1992
Plourde PV, Dyroff M, Dukes M: Arimidex: A potent and selective fourth-generation aromatase inhibitor. Br Cancer Res Treat 30: 103–111, 1994
Yates RA, Dowsett M, Fisher GV, Selen A, Wyld PJ: Arimidex (ZD 1033): a selective, potent inhibitor of aromatase in postmenopausal female volunteers. Br J Cancer 73: 543–548, 1996
Plourde PV, Dyroff M, Dowsett M, Demers L, Yates R, Webster A: Arimidex: A new oral, once-a-day aromatase inhibitor. J Steroid Biochem Mol Biol 53: 175–179, 1995
Plourde PV, Yates RA, Dyroff M, Dukes M, Dowsett M, Demers LM, Webster A: The effect of arimidex, a new potent aromatase inhibitor, on circulating estrogens in postmenopausal women. Proc Am Assoc Clin Oncol 12 (Abstr 165): 91, 1993
Lønning PE, Helle SI, Johannessen DC, Adlercreutz H, Lien EA, Tally M, Ekse D, Fotsis T, Anker GB, Hall K: Relations between sex hormones, sex hormone binding globulin, insulin-like growth facort-I and insulin-like growth factor binding protein-1 in post-menopausal breast cancer patients. Clin Endocrinol 42: 23–30, 1995
Jacobs S, Lønning PE, Haynes B, Griggs L, Dowsett M: Measurement of aromatisation by a urine technique suitable for the evaluation of aromatase inhibitors in vivo. J Enzyme Inhibition 4: 315–325, 1991
Dowsett M, Jones A, Johnston SRD, Jacobs S, Trunet P, Smith IE: In vivo measurement of aromatase inhibition by letrozole (CGS 20267) in post menopausal patients with breast cancer. Clin Cancer Res 1: 1511–1515, 1995
Geisler J, King N, Dowsett M, Ottestad L, LUndgren S, Walton P, Kormeset PO, Lønning PE: 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 74: 1286–1291, 1996
Lønning PE, Ekse D: A sensitive assay for measurement of plasma estrone sulphate in patients on treatment with aromatasc inhibitors. J Steroid Biochem Mol Biol 55: 409–412, 1995
Geisler J, Johannessen DC, Anker G, Lønning PE: Treatment with formestane alone and in combination with aminoglutethimide in heavily pretreated cancer patients: Clinical and endocrine effects. Eur J Cancer 32A: 789–792, 1996
Jonat W, Howell A, Blomqvist C, Eiermann W, Winblad G, Tyrrell C, Mauriac L, Roche H, Lundgren S, Hellmund R, Azab M: A randomized trial comparing two doses of the new selective aromatase inhibitor anastrozole (arimidex) with megestrol acetate in postmenopausal patients with advanced breast cancer. Eur J Cancer 32A: 404–412, 1996
Buzdar AU, Jones SE, Vogel CL, Wolter J, Plourde P, Webster A: A phase III trial comparing anastrozole (1 and 10 mil ligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma. Cancer 79: 730–739, 1997
Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, Eiermann W, Wolter JM, Azab M, Webster A, Plourde PV: 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. J Clin Oncol 14: 2000–2011, 1996
Jonat W, Buzdar A, Howell A, Webster A, Strutt K: Significantly improved survival with arimidex (anastrozole) compared with megestrol acetate (MA) in postmenopausal women with advanced breast cancer (ABC). Updated results of two randomized trials. Eur J Cancer 33 (Abstr 644): S.145, 197
Lundgren S, Helle SI, Lønning PE: Profound suppression of plasma estrogens by megestrol acetate in postmenopausal breast cancer patients. Clin Cancer Res 2: 1515–1521, 1996
Reed MJ, Topping L, Coldham NG, Purohit A, Ghilchik MW, James VHT: Control of aromatase activity in breast cancer cells: The role of cytokines and growth facotrs. J Steroid Biochem Mol Biol 44: 589–596, 1993
Reed MJ, Aherne GW, Ghilchik MW, Patel S, Chakraborty J: Concentrations of oestrone and 4-hydroxyandrostenedione in malignant and normal breast tissue. Int J Cancer 49: 562–565, 1991
de Jong PC, van de Ven J, Nortier HWR, Maitimu-Smeele I, Donker TH, Thijssen JHH, Slee PHTJ, Blankenstein RA: Inhibition of breast cancer tissue aromatase activity and estrogen concentrations by the third-generation aromatase inhibitor vorozole. Cancer Res 57: 2109–2111, 1997
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lønning, P.E., Geisler, J. & Dowsett, M. Pharmacological and clinical profile of anastrozole. Breast Cancer Res Treat 49 (Suppl 1), S53–S57 (1998). https://doi.org/10.1023/A:1006000806630
Issue Date:
DOI: https://doi.org/10.1023/A:1006000806630