An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane

Cancer

Volumn 95, Issue 9, 2002, Pages 2006-2016

  Buzdar, Aman U ^a   Robertson, John F R ^b   Eiermann, Wolfgang ^a   Nabholtz, Jean Marc ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b NOTTINGHAM CITY HOSPITAL   (United Kingdom)

Author keywords

Anastrozole; Aromatase inhibitor; Breast carcinoma; Estrogen; Exemestane; Letrozole; Postmenopausal

Indexed keywords

ALDOSTERONE; ANASTROZOLE; AROMATASE INHIBITOR; ESTROGEN; EXEMESTANE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROCORTISONE; LETROZOLE; LIPID; LOW DENSITY LIPOPROTEIN; STEROID; TAMOXIFEN;

ACNE; ADVANCED CANCER; ALDOSTERONE BLOOD LEVEL; ANDROGEN METABOLISM; ARTICLE; BREAST CANCER; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CLINICAL TRIAL; DRUG ANTAGONISM; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG HALF LIFE; DRUG METABOLISM; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; DYSLIPIDEMIA; FEMALE; HUMAN; HYDROCORTISONE BLOOD LEVEL; HYPERTRICHOSIS; LIPID BLOOD LEVEL; LONG TERM CARE; OSTEOLYSIS; OSTEOPOROSIS; POSTMENOPAUSE; PRIORITY JOURNAL; SIDE EFFECT; STEROIDOGENESIS; WEIGHT GAIN;

ANDROSTADIENES; ANTINEOPLASTIC AGENTS; AROMATASE INHIBITORS; BREAST NEOPLASMS; ENZYME INHIBITORS; FEMALE; HUMANS; NITRILES; TRIAZOLES;

EID: 0036839717     PISSN: 0008543X     EISSN: None     Source Type: Journal    
DOI: 10.1002/cncr.10908     Document Type: Article

References (62)

1. Lynn AG, Ries MS. Top 5 cancers for females and males in the US. J Natl Cancer Inst. 1995;87:867.
2. Jemal A, Thomas A, Murray T, Thun M. Cancer statistics, 2002. CA Cancer J Clin. 2002;52:23-47.
3. Howe HL, Wingo PA, Thun MJ, et al. Annual report to the nation on the status of cancer (1973 through 1998), featuring cancers with recent increasing trends. J Natl Cancer Inst. 2001;93:824-842.
4. Theobald AJ. Management of advanced breast cancer with endocrine therapy: The role of the primary healthcare team. Int J Clin Pract. 2000;54:665-669.
5. Masamura S, Adlercreutz H, Harvey H, et al. Aromatase inhibitor development for the treatment of breast cancer. Breast Cancer Treat. 1995;33:19-26.
6. Cheung K-L, Forward D, Jackson L, Robertson J. The combined use of goserelin and anastrozole as second line endocrine therapy in premenopausal women with advanced breast cancer - A study of its clinical and endocrine effects [abstract 19371. Proc Am Soc Clin Oncol. 2001;20:47b.
7. Wells SA, Santen RT, Lipton A, et al. Medical adrenalectomy with aminoglutethimide clinical studies in postmenopausal patients with metastatic breast carcinoma. Ann Surg. 1978;187:475-484.
8. Goss PE, Powles TJ, Dowsett M, et al. Treatment of advanced postmenopausal breast cancer with the aromatase inhibitor, 4-hydroxyandrostenedione: Phase II report. Cancer Res. 1986;46:4823-4826.
9. Buzdar A, Jonat W, Howell A, et al. 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. 1996;14:2000-2011.
10. Kaufmann M, Bajetta E, Dirix LY, et al. Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: Results of a Phase III randomized double-blind trial. J Clin Oncol. 2000;18:1399-1411.
11. Buzdar AU, Jonat W, Howell A, et al., for the Arimidex Study Group. Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma. Results of a survival update based on a combined analysis of data from two mature Phase III trials. Cancer. 1998;83:1142-1152.
12. Dombernowsky P, Smith I, Falkson R, et al. Letrozole, a new oral aromatase inhibitor for advanced breast cancer: Double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate. J Clin Oncol. 1998;16:453-461.
13. Buzdar A, Douma J, Davidson N, et al. Phase III, multicenter, double-blind, randomized study of letrozole (Femara™), an aromatase inhibitor, for advanced breast cancer versus megestrol acetate conducted in the United States, Canada, Denmark, Germany, Italy, Netherlands, and the United Kingdom. J Clin Oncol. 2001;19:3357-3366.
14. Gershanovich M, Chaudri HA, Campos D, et al. Letrozole, a new oral aromatase inhibitor: Randomised trial comparing 2.5 mg daily, with 0.5 mg daily and aminoglutethimide in postmenopausal women with advanced breast cancer. Ann Oncol. 1998;9:639-645.
15. Nabholtz JM, Buzdar A, Pollak M, et al. Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: Results of a North American multicenter randomized trial. J Clin Oncol. 2000;18:3758-3767.
16. Bonneterre J, Buzdar A, Nabholtz JM, et al. Anastrozole ("Arimidex") is superior to tamoxifen as first-line therapy in hormone receptor-positive advanced breast cancer: Results of two randomized trials designed for combined analysis. Cancer. 2001;92:2247-2258.
17. Milla-Santos A, Milla L, Rallo L, Solano V. Anastrozole versus tamoxifen in hormone dependent advanced breast cancer. A Phase II randomized trial [abstract 173]. Breast Cancer Res Treat. 2000;64:54.
18. Mouridsen H, Gershanovich M, Sun Y, et al. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: Results of a Phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol. 2001;19:2596-2560.
19. Eiermann W, Paepke S, Appfelstaedt J, et al. Preoperative treatment of postmenopausal breast cancer patients with letrozole. A randomized double-blind multicenter study. Ann Oncol. 2001;12:1572-1532.
20. Dirix L, Piccart MJ, Lohrisch C, et al. Efficacy of and tolerance to exemestane (E) versus tamoxifen (T) in first-line hormone therapy (HT) of postmenopausal metastatic breast cancer (MBC) patients (pts): A European Organisation for the Research and Treatment of Cancer (EORTC Breast Group) Phase II trial with Pharmacia and Upjohn [abstract 114]. Proc Am Soc Clin Oncol. 2001;20(Part 1):29a.
21. Michaud LB, Buzdar AU. Risks and benefits of aromatase inhibitors in postmenopausal breast cancer. Drug Safety. 1999;21:297-309.
22. Bajetta E, Zilembo N, Noberasco C, et al. The minimal effective exemestane dose for endocrine activity in advanced breast cancer. Eur J Cancer. 1997;33:587-591.
23. Jones S, Vogel C, Arkhipov A, et al. Multicenter, Phase II trial of exemestane as third-line hormonal therapy of postmenopausal women with metastatic breast cancer. J Clin Oncol. 1999;17:3418-3425.
24. Goss PE, Strasser K. Aromatase inhibitors in the treatment and prevention of breast cancer. J Clin Oncol. 2001;19:881-894.
25. 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. 1995;53:175-179.
26. Demers LM, Lipton A, Harvey HA, et al. The efficacy of CGS 20267 in suppressing estrogen biosynthesis in patients with advanced stage breast cancer. J Steroid Biochem Mol Biol. 1993;44:687-691.
27. Zilembo N, Noberasco C, Bajetta E, et al. Endocrinological and clinical evaluation of exemestane, a new steroidal aromatase inhibitor. Br J Cancer. 1995;72:1007-1012.
28. Camp-Sorrell D. Anastrozole: An effective, second-line hormonal treatment for advanced breast cancer. Cancer Pract. 1997;5:391-393.
29. Clemett N, Lamb NM. Exemestane: A review of its use in postmenopausal women with advanced breast cancer. Drugs. 2000;59:1279-1296.
30. Bajetta E, Zilembo N, Dowsett M, et al. Double-blind, randomised, multicentre endocrine trial comparing two letrozole doses, in postmenopausal breast cancer patients. Eur J Cancer. 1999;35:208-213.
31. Bisagni G, Cocconi G, Scaglione F, Fraschini F, Pfister C, Trunet PF. Letrozole, a new oral non-steroidal aromatase inhibitor in treating postmenopausal patients with advanced breast cancer. A pilot study. Ann Oncol. 1996;7:99-102.
32. Yates RA, Dowsett M, Fisher GV, Selen A, Wyld PJ. Arimidex (ZD1033): A selective, potent inhibitor of aromatase in postmenopausal female volunteers. Br J Cancer. 1996;73:543-548.
33. Spinelli R, Jannuzzo MG, Poggesi I, et al. Pharmacokinetics (PK) of Aromasin® (exemestane, EXE) after single and repeated doses in healthy postmenopausal volunteers (HPV) [abstract 1185]. Eur J Cancer. 1999;35(Suppl 4):S295.
34. Anonymous. Toremifene and letrozole for advanced breast cancer. Med Lett Drugs Ther. 1998;40:43-45.
35. Sioufi A, Sandrenan N, Godbillon J, et al. Comparative bioavailability of letrozole under fed and fasting conditions in 12 healthy subjects after 2.5 mg single oral administration. Biopharmaceutics Drug Disp. 1997;18:489-497.
36. Geisler J, King N, Dowsett M, et al. Influence of anastrozole (Arimidex), a selective, non-steroidal aromatase inhibitor, or in vivo aromatization and plasma estrogen levels in postmenopausal women with breast cancer. Br J Cancer. 1996;74:1286-1291.
37. Geisler J, Anker G, Dowsett M, Lonning PE. Letrozole suppresses plasma estrogen levels in postmenopausal breast cancer patients more completely than anastrozole [abstract 394]. Proc Am Soc Clin Oncol. 2000;19:102a.
38. Geisler J, Bernsten L, Ottestad B, Lindtjorn B, Dowsett M, Lonning PE. Neoadjuvant treatment with anastrozole (Arimidex) causes profound suppression of intra-tumor estrogen levels [abstract 311]. Proc Am Soc Clin Oncol. 1999;18:82a.
39. Miller WR. Biology of aromatase inhibitors: Pharmacology/endocrinology within the breast. Endocr Relat Cancer. 1999;6:187-195.
40. Dixon JM, Grattage L, Renshaw L, Miller WR. Exemestane as neoadjuvant treatment for locally advanced breast cancer: Endocrinologic and clinical endpoints [abstract 170]. Breast Cancer Res Treat. 2000;64:53.
41. Grimm SW, Dyrof MC. Inhibition of human metabolizing cytochromes P450 by anastrozole, a potent and selective inhibitor of aromatase. Drug Metab Disp. 1997;25:598-602.
42. Wirz B, Valles B, Parkinson A, et al. CYP3A4 and CYP2A6 are involved in the biotransformation of letrozole (Femara). Seventh North American ISSX Meeting. 1996;10:359.
43. Anonymous. Exemestane for advanced breast cancer. Med Lett Drugs Ther. 2000;42:35-36.
44. St Peter J, Thyrum P, Yeh C, Dyroff M, Selen A. Lack of effect of anastrozole, an aromatase inhibitor, on antipyrine pharmacokinetics in postmenopausal women [abstract PII-27]. Clin Pharm Ther. 1997;61:172.
45. Yates RA, Wong J, Seiberling M, et al. The effect of anastrozole on the single-dose pharmacokinetics and anticoagulantactivity of warfarin in healthy volunteers. Br J Clin Pharmacol. 2001;51:429-435.
46. The ATAC Trialists' Group. Pharmacokinetics of anastrozole and tamoxifen alone, and in combination, during adjuvant endocrine therapy for early breast cancer in postmenopausal women: a sub-protocol of the "Arimidex™ and tamoxifen alone or in combination" (ATAC) trial. Br J Cancer. 2001;85:317-324.
47. Dowsett M, Pfister C, Johnson SRD, et al. Impact of tamoxifen on the pharmacokinetics and endocrine effects of the aromatase inhibitor letrozole in postmenopausal women with breast cancer. Clin Cancer Res. 1999;5:2338-2343.
48. Kannel WB, Wilson WF. Comparison of risk profiles for cardiovascular events: Implications for prevention. In: Schrier RW, Baxter JD, Ozau VJ, Fauci AS, Abboud FM, editors. Advances in Internal Medicine, vol. 43. St. Louis: Mosby-Year Book, Inc., 1997:39-66.
49. Dewar J, Nabholtz J-M, Bonneterre J, et al. The effect of anastrozole (Arimidex™) on serum lipids - Data from a randomized comparison of anastrozole (AN) versus tamoxifen (TAM) in postmenopausal (PM) women with advanced breast cancer (ABC) [abstract 164]. Breast Cancer Res Treat. 2001;69:224.
50. Wojtacki J, Kruszewski WJ, Les'niewski-Kmak K, et al. Short-term effects of anastrozole therapy on serum lipid profile in patients with breast cancer, previously treated with tamoxifen. Preliminary Report Nowotwory. 2001;51:43-47.
51. Elisaf MS, Bairaktari ET, Nicolaides C, et al. Effect of letrozole on the lipid in postmenopausal women with breast cancer. Eur J Cancer. 2001;37:1510-1513.
52. Engan T, Krane J, Johannessen DC, Kvinnsland S. Plasma changes in breast cancer patients during endocrine therapy-lipid measurements and nuclear magnetic resonance (NMR) spectroscopy. Breast Cancer Res Treat. 1995;36:287-297.
53. Lohrisch C, Paridaens R, Dirix LY, et al. No adverse impact on serum lipids of the irreversible aromatase inactivator Aromasin® [Exemestane (E)] in first-line treatment of metastatic breast cancer (MBC),: Companion study to a European Organization of Research and Treatment of Cancer (Breast Group) Trial with Pharmacia Upjohn [abstract 167]. Proc Am Soc Clin Oncol. 2001;20:43a.
54. Plourde PV, Dyroff M, Dukes M. Arimidex™: A potent and selective fourth-generation aromatase inhibitor. Breast Cancer Res Treat. 1994;30:103-111.
55. Buzdar A and Esparza-Guerra L. Anastrozole "Arimidex™" does not impair adrenal cortisol or aldosterone synthesis in postmenopausal women with advanced breast cancer [abstract 1954]. Proc Am Soc Clin Oncol. 2001;20:52b.
56. Wolter J, Robert J, Harvey N, Berkowitz I, Plourde PV. Arimidex (ZD1033): A Phase I study of a new, selective orally active aromatase inhibitor in postmenopausal women with advanced breast cancer [abstract 175]. Proc Am Soc Clin Oncol. 1995;14:199.
57. Evans TRJ, di Salle E, Ornati G, et al. Phase I and endocrine study of exemestane (FCE 1243040), a new aromatase inhibitor, in postmenopausal women. Cancer Res. 1992;52:5933-5939.
58. Goss P, Grynpas M, Qi S, Hu H. The effects of exemestane on bone and lipids in the ovariectomized rat [abstract 132]. Breast Cancer Res Treat. 2000;64:51.
59. Heshmati HM, Khosla S, Robins SP, Geller N, McAlister CA, Riggs BL. Endogenous residual estrogen levels determine bone resorption even in late postmenopausal women [abstract 76]. J Bone Mineral Res. 1997;12(Suppl 1):S121.
60. Lai JM, Taxel P, Raisz LG. The effect of aromatase inhibition on bone turnover in older men [abstract P251]. J Am Geriatr Soc. 1998;46:S79.
61. Harper-Wynne C, Ross G, Sacks N, Gui G, Dowsett M. Effects of the aromatase inhibitor letrozole in healthy postmenopausal women rationale for prevention [abstract 3091]. Proc Am Soc Clin Oncol. 2001;20:335b.
62. Di Salle E, Ornati G, Giudici D, et al. Exemestane, (FCE24304) a new steroidal aromatase inhibitor. J Steroid Biochem Mol Biol. 1992;43:137-143.