Skip to main content
SpringerLink
Log in

Letrozole

A Review of its Use in Postmenopausal Women with Breast Cancer

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Summary

Abstract

Letrozole (Femara®), a nonsteroidal, third-generation aromatase inhibitor administered orally once daily, has shown efficacy in the treatment of postmenopausal women with early-stage or advanced, hormone-sensitive breast cancer.

In early-stage disease, extending adjuvant endocrine therapy with letrozole (beyond the standard 5-year period of tamoxifen) improved disease-free survival; compared with placebo there was a 43% relative reduction in disease recurrences or new contralateral breast tumours at a median follow-up of 2.4 years. The results of 4 months’ neoadjuvant treatment with letrozole or tamoxifen in postmenopausal women with untreated primary disease favour letrozole.

In advanced breast cancer, letrozole was superior to tamoxifen as first-line treatment; time to disease progression was significantly longer (9.4 vs 6.0 months, p < 0.0001) and objective response rate was significantly greater with letrozole, but median overall survival was similar between groups. For second-line therapy of advanced breast cancer that had progressed on antiestrogen therapy, letrozole showed efficacy equivalent to that of anastrozole and similar to or better than that of megestrol acetate.

Letrozole is generally well tolerated and has a similar tolerability profile to tamoxifen; the most common treatment-related adverse events were hot flushes, nausea and hair thinning. In patients with tumours that had progressed on antiestrogen therapy, letrozole was tolerated as least as well as, or better than, anastrozole or megestrol acetate. In the trial of extended adjuvant therapy, adverse events reported more frequently with letrozole than placebo were hot flushes, arthralgia, myalgia and arthritis. The long-term effects of letrozole on bone mineral density or lipid profile have not been determined and these parameters may require monitoring.

In several pharmacoeconomic modelling studies from various public healthcare system perspectives, letrozole was considered a cost effective choice for first-line (vs tamoxifen) or second-line (vs megestrol acetate) treatment for advanced breast cancer in postmenopausal women.

In conclusion, letrozole 2.5 mg/day is effective in the treatment of postmenopausal women with early-stage or advanced breast cancer. The efficacy, cost effectiveness and favourable tolerability profile of letrozole are reflected in current treatment guidelines recommending the drug as first-line therapy for advanced breast cancer. Letrozole is superior to tamoxifen for first-line treatment and is at least as effective as standard second-line treatments in disease that has progressed on antiestrogen therapy. For early-stage disease, letrozole is superior to tamoxifen in the neoadjuvant setting, and prolongs disease-free survival when administered after the standard 5-year period of adjuvant tamoxifen therapy.

Overview of Pharmacological Properties

Letrozole is a highly specific, nonsteroidal aromatase inhibitor and a potent inhibitor of estrogen synthesis. Plasma levels of estrone, estradiol and estrone sulfate were significantly reduced by letrozole in postmenopausal women with breast cancer. Letrozole had anti-tumour effects in ovariectomised mouse models of postmenopausal estrogen-dependent breast cancer, and it reduced cellular markers of proliferation more than tamoxifen in estrogen-dependent tumours that overexpressed human epidermal growth factor receptor (HER)1 and/or HER2. Levels of bone resorption markers were increased with letrozole in healthy postmenopausal women and those with a history of breast disease.

In postmenopausal women with breast cancer, letrozole is rapidly and almost completely absorbed from the gastrointestinal tract. Food has no clinically significant effect on the absorption. The mean maximum plasma concentration following a single oral 2.5mg dose was 107 nmol/L and was reached after a median of ≈2 hours. Steady-state plasma concentrations were attained after approximately 40 days.

Letrozole is about 60% plasma-protein bound and has a large volume of distribution (1.87 L/kg). The drug is metabolised via the cytochrome P450 enzyme system and is excreted mainly in the urine. The mean elimination half-life was 82 hours.

Concurrent administration of tamoxifen and letrozole reduced the plasma levels of letrozole compared with those of letrozole administered alone.

Therapeutic Use

Letrozole 2.5 mg/day (administered to postmenopausal women participating in randomised, double-blind studies) has efficacy as first- and second-line hormonal therapy in advanced breast cancer and as adjuvant and neoadjuvant therapy in early-stage breast cancer.

Extended adjuvant therapy (randomised and double-blind) with letrozole following the standard 5 years of adjuvant tamoxifen or antiestrogen therapy improved disease-free survival compared with placebo in postmenopausal women with early-stage primary breast cancer. Early beneficial effects of letrozole prompted the unblinding of this trial at a median of 2.4 years, although patients receiving letrozole will still be monitored for the planned 5-year study period.

The results of 4 months’ randomised and double-blind neoadjuvant treatment with letrozole or tamoxifen in postmenopausal women with untreated early-stage primary disease favour letrozole; the letrozole group had a greater objective response rate and more letrozole recipients underwent breast-conserving surgery compared with tamoxifen recipients.

In advanced breast cancer, letrozole was superior to tamoxifen as first-line treatment in a large, well controlled clinical study in which approximately half of the patients in each group crossed over to the other therapy on disease progression. Time to disease progression (primary endpoint) was longer with letrozole than tamoxifen (9.4 vs 6.0 months, p < 0.0001) and the objective response rate was also greater. Median overall survival was similar between groups.

Large randomised trials of second-line therapy (following antiestrogen therapy) in postmenopausal women with advanced breast cancer indicated that letrozole was at least as effective as anastrozole or megestrol acetate for primary endpoints and was superior for some secondary endpoints.

Pharmacoeconomic Studies

Pharmacoeconomic modelling studies conducted from the perspective of North American or European public healthcare systems indicate that letrozole was cost effective for first-line (compared with tamoxifen) or second-line (compared with megestrol acetate) treatment for advanced breast cancer in postmenopausal women. These studies considered direct costs and used data inputs from clinical trials, the published literature and expert opinion. Incremental costs per life-year or quality-adjusted life-year (QALY) gained with letrozole were well below generally accepted thresholds for cost effectiveness; incremental costs per QALY gained for letrozole as first-line treatment (relative to tamoxifen) were $Canl2 500, £2927–£3969 or £8514 and per life-year gained for the drug as second-line treatment (relative to megestrol acetate) were $Can9000, $Can5051 or £3588.

Tolerability

In large trials in postmenopausal women with early-stage or advanced breast cancer, letrozole was at least as well tolerated as tamoxifen, anastrozole and megestrol acetate and had a similar adverse events profile to tamoxifen and anastrozole. Data from several studies indicated that the most common treatment-related adverse events with letrozole were hot flushes 5–20%, nausea 5–11% and headache 7–11%. The following adverse events were reported in only one study: fatigue 5%, peripheral oedema 6%, dyspnoea 10% and back pain 15%.

Adverse events occurring significantly more frequently with letrozole than placebo (when administered as extended adjuvant therapy following tamoxifen therapy) were hot flushes, arthralgia, myalgia and arthritis. Vaginal bleeding occurred less frequently with letrozole than with placebo.

The most commonly occurring treatment-related adverse events with letrozole or tamoxifen during first-line treatment for advanced disease or as neoadjuvant therapy in primary untreated disease were hot flushes, nausea and hair thinning (incidence similar in both groups). The incidence of thromboembolic events was similar between groups.

Letrozole was tolerated as well as or better than anastrozole or megestrol acetate in trials of postmenopausal women with breast cancer that had been treated with an antiestrogen.

There are no long-term data on the effects of letrozole therapy on bone mineral density and blood lipid levels; monitoring of these parameters in women on long-term therapy is prudent.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III
Table IV
Table V
Fig. 1

Similar content being viewed by others

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Beslija S, Bonneterre J, Burstein HJ, et al. Consensus on medical treatment of metastatic breast cancer. Breast Cancer Res Treat 2003; 81 Suppl. 1: S1–7

    Article  Google Scholar 

  2. Simon MS, Ibrahim D, Newman L, et al. Efficacy and economics of hormonal therapies for advanced breast cancer. Drugs Aging 2002; 19(6): 453–63

    Article  PubMed  CAS  Google Scholar 

  3. Buzdar AU. Advances in endocrine treatments for postmenopausal women with metastatic and early breast cancer. Oncologist 2003; 8(4): 335–41

    Article  PubMed  CAS  Google Scholar 

  4. Come SE, Buzdar AU, Arteaga CL, et al. Second international conference on recent advances and future directions in endocrine manipulation of breast cancer: summary consensus statement. Clin Cancer Res 2003 Jan; 9 Suppl.: 443s–6s

    PubMed  Google Scholar 

  5. Pritchard KI. Endocrine therapy of advanced disease: analysis and implications of the existing data. Clin Cancer Res 2003 Jan; 9 (1 Pt 2): 460s–7s

    PubMed  CAS  Google Scholar 

  6. Smith IE, Dowsett M. Aromatase inhibitors in breast cancer. N Engl J Med 2003 Jun 12; 348(24): 2431–42

    Article  PubMed  CAS  Google Scholar 

  7. Brodie A. Aromatase inhibitor development and hormone therapy: a perspective. Semin Oncol 2003 Aug; 30 (4 Suppl. 14): 12–22

    Article  PubMed  CAS  Google Scholar 

  8. Novartis Pharma AG. Letrozole PDR information [online]. Available from URL: http://www.drugs.com [Accessed 2004 Mar 1]

  9. Novartis Pharmaceuticals Canada Inc. Health Canada confirms that women being treated for advanced breast cancer can live longer and better when taking Femara® [media release]. 2003

  10. Goss PE, Ingle JN, Martino S, et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 2003 Nov 6; 349(19): 1793–802

    Article  PubMed  CAS  Google Scholar 

  11. Keating GM, Jarvis B. Letrozole: an updated review of its use in postmenopausal women with advanced breast cancer. Am J Cancer 2002; 1(5): 351–71

    Article  CAS  Google Scholar 

  12. Lamb HM, Adkins JC. Letrozole: a review of its use in postmenopausal women with advanced breast cancer. Drugs 1998; 56(6): 1125–40

    Article  PubMed  CAS  Google Scholar 

  13. Shaw HS, Ellis MJ. Letrozole in the treatment of breast cancer. Expert Opin Pharmacother 2002 May; 3(5): 607–17

    Article  PubMed  CAS  Google Scholar 

  14. Haynes BP, Dowsett M, Miller WR, et al. The pharmacology of letrozole. J Steroid Biochem Mol Biol 2003 Oct; 87(1): 35–45

    Article  PubMed  CAS  Google Scholar 

  15. Lonning PE. Clinical pharmacokinetics of aromatase inhibitors and inactivators. Clin Pharmacokinet 2003; 42(7): 619–31

    Article  PubMed  CAS  Google Scholar 

  16. Lonning P, Pfister C, Martoni A, et al. Pharmacokinetics of third-generation aromatase inhibitors. Semin Oncol 2003 Aug; 30 (4 Suppl. 14): 23–32

    Article  PubMed  CAS  Google Scholar 

  17. Njar VC, Brodie AM. Comprehensive pharmacology and clinical efficacy of aromatase inhibitors. Drugs 1999; 58(2): 233–55

    Article  PubMed  CAS  Google Scholar 

  18. Iveson TJ, Smith IE, Ahern J, et al. Phase I study of the oral nonsteroidal aromatase inhibitor CGS 20267 in healthy postmenopausal women. J Clin Endocrinol Metab 1993; 77: 324–31

    Article  PubMed  CAS  Google Scholar 

  19. Demers LM. Effects of fadrozole (CGS 16949A) and letrozole (CGS 20267) on the inhibition of aromatase activity in breast cancer patients. Breast Cancer Res Treat 1994; 30(1): 95–102

    Article  PubMed  CAS  Google Scholar 

  20. Iveson TJ, Smith IE, Ahern J, et al. Phase I study of the oral nonsteroidal aromatase inhibitor CGS 20267 in postmenopausal patients with advanced breast cancer. Cancer Res 1993; 53: 266–70

    PubMed  CAS  Google Scholar 

  21. Bhatnagar AS, Batzl C, Häusler A, et al. Pharmacology of nonsteroidal aromatase inhibitors. In: Pasqualini JR, Katzenellenbogen BS, editors. Hormone-dependent cancer. New York: Marcel Dekker, Inc., 1996: 155–68

    Google Scholar 

  22. Dowsett M, Jones A, Johnston SR, et al. In vivo measurement of aromatase inhibition by letrozole (CGS 20267) in postmenopausal patients with breast cancer. Clin Cancer Res 1995; 1: 1511–5

    PubMed  CAS  Google Scholar 

  23. Geisler J, Haynes B, Anker G, et al. Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study. J Clin Oncol 2002 Feb 1; 20(3): 751–7

    Article  PubMed  CAS  Google Scholar 

  24. Miller WR. Biology of aromatase inhibitors: pharmacology/ endocrinology within the breast. Endocr Relat Cancer 1999; 6: 187–95

    Article  PubMed  CAS  Google Scholar 

  25. Miller WR, Dixon JM. Local endocrine effects of aromatase inhibitors within the breast. J Steroid Biochem Mol Biol 2001 Dec; 79(1–5): 93–102

    Article  PubMed  CAS  Google Scholar 

  26. Lipton A, Demers LM, Harvey HA, et al. Letrozole (CGS 20267): a phase I study of a new potent oral aromatase inhibitor of breast cancer. Cancer 1995; 75: 2132–8

    Article  PubMed  CAS  Google Scholar 

  27. Klein KO, Demers LM, Santner SJ, et al. Use of ultrasensitive recombinant cell bioassay to measure estrogen levels in women with breast cancer receiving the aromatase inhibitor, letrozole. J Clin Endocrinol Metab 1995; 80(9): 2658–60

    Article  PubMed  CAS  Google Scholar 

  28. Lu Q, Yue W, Wang J, et al. The effects of aromatase inhibitors and antiestrogens in the nude mouse model. Breast Cancer Res Treat 1998; 50: 63–71

    Article  PubMed  CAS  Google Scholar 

  29. Brodie A, Lu Q, Yue W, et al. Intratumoral aromatase model: the effects of letrozole (CGS 20267). Breast Cancer Res Treat 1998; 49 Suppl. 1: S23–6

    Article  PubMed  CAS  Google Scholar 

  30. Yue W, Wang J, Savinov A, et al. Effect of aromatase inhibitors on growth of mammary tumors in a nude mouse model. Cancer Res 1995; 55: 3073–7

    PubMed  CAS  Google Scholar 

  31. Lu Q, Liu Y, Long BJ, et al. The effect of combining aromatase inhibitors with antiestrogens on tumor growth in a nude mouse model for breast cancer. Breast Cancer Res Treat 1999; 57: 183–92

    Article  PubMed  CAS  Google Scholar 

  32. Long BJ, Jelovac D, Thiantanawat A, et al. The effect of second-line antiestrogen therapy on breast tumor growth after first-line treatment with the aromatase inhibitor letrozole: long-term studies using the intratumoral aromatase postmenopausal breast cancer model. Clin Cancer Res 2002 Jul; 8(7): 2378–88

    PubMed  CAS  Google Scholar 

  33. Thiantanawat A, Long BJ, Brodie AM. Signaling pathways of apoptosis activated by aromatase inhibitors and antiestrogens. Cancer Res 2003 Nov 15; 63(22): 8037–50

    PubMed  CAS  Google Scholar 

  34. Lee K, Macaulay VM, Nicholls JE, et al. An invivomodel of intratumoural aromatase using aromatase-transfected MCF7 human breast cancer cells. Int J Cancer 1995; 62(3): 297–302

    Article  PubMed  CAS  Google Scholar 

  35. Ellis MJ, Coop A, Singh B, et al. Letrozole inhibits tumor proliferation more effectively than tamoxifen independent of HER1/2 expression status. Cancer Res 2003 Oct 1; 63(19): 6523–31

    PubMed  CAS  Google Scholar 

  36. Heshmati HM, Khosla S, Robins SP, et al. Role of low levels of endogenous estrogen in regulation of bone resorption in late postmenopausal women. J Bone Miner Res 2002 Jan; 17(1): 172–8

    Article  PubMed  CAS  Google Scholar 

  37. Harper-Wynne C, Ross G, Sacks N, et al. Effects of the aromatase inhibitor letrozole on normal breast epithelial cell proliferation and metabolic indices in postmenopausal women: a pilot study for breast cancer prevention. Cancer Epidemiol Biomarkers Prev 2002 Jul; 11(7): 614–21

    PubMed  CAS  Google Scholar 

  38. Elisaf MS, Bairaktari ET, Nicolaides C, et al. Effect of letrozole on the lipid profile in postmenopausal women with breast cancer. Eur J Cancer 2001; 37: 1510–3

    Article  PubMed  CAS  Google Scholar 

  39. Pfister CU, Martoni A, Zamagni C, et al. Effect of age and single versus multiple dose pharmacokinetics of letrozole (Femara) in breast cancer patients. Biopharm Drug Dispos 2001 Jul; 22(5): 191–7

    Article  PubMed  CAS  Google Scholar 

  40. Sioufi A, Gauducheau N, Pineau V, et al. Absolute bioavailability of letrozole in healthy postmenopausal women. Biopharm Drug Dispos 1997; 18(9): 779–89

    Article  PubMed  CAS  Google Scholar 

  41. Sioufi A, Sandrenan N, Godbillon J, et al. Comparative bioavailability of letrozole under fed and fasting conditions in 12 healthy subjects after a 2.5 mg single oral administration. Biopharm Drug Dispos 1997; 18(6): 489–97

    Article  PubMed  CAS  Google Scholar 

  42. Colussi DM, Parisot CY, Lefevre GY. Plasma protein binding of letrozole, a new nonsteroidal aromatase enzyme inhibitor. J Clin Pharmacol 1998; 38: 727–35

    PubMed  CAS  Google Scholar 

  43. WirzB, Valles B, Parkinson A, et al. CYP3A4 and CYP2A6 are involved in the biotransformation of letrozole (®Femara) [abstract no. 359]. 7th North American Meeting of the International Society for the Study of Xenobiotics; 1996 20–24 Oct; San Diego

  44. Ingle JN, Suman VJ, Johnson PA, et al. Evaluation of tamoxifen plus letrozole with assessment of pharmacokinetic interaction in postmenopausal women with metastatic breast cancer. Clin Cancer Res 1999; 5: 1642–9

    PubMed  CAS  Google Scholar 

  45. Dowsett M, Pfister C, Johnston SR, 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: 2338–43

    PubMed  CAS  Google Scholar 

  46. Morgan JM, Palmisano M, Spencer S, et al. Pharmacokinetic effect of cimetidine on a single 2.5 mg dose of letrozole in healthy subjects [abstract no. 26]. J Clin Pharmacol 1996; 36: 852

    Google Scholar 

  47. 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 Nov; 12(11): 1527–32

    Article  PubMed  CAS  Google Scholar 

  48. Mouridsen H, Gershanovich M, Sun Y, et al. Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. J Clin Oncol 2003 Jun 1; 21(11): 2101–9

    Article  PubMed  CAS  Google Scholar 

  49. 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 May 15; 19(10): 2596–606

    PubMed  CAS  Google Scholar 

  50. Mouridsen H, Sun Y, Gershanovich M, et al. Significantly longer time to progression for Femara® (letrozole) in patients with or without prior adjuvant tamoxifen: updated analysis of the double-blind, randomized, multinational phase III trial of letrozole compared to tamoxifen as first-line hormonal therapy for advanced breast cancer [abstract no. 256]. 25th Annual San Antonio Breast Cancer Symposium; 2002 Dec 11–14; San Antonio

  51. Smith IE. Letrozole versus tamoxifen in the treatment of advanced breast cancer and as neoadjuvant therapy. J Steroid Biochem Mol Biol 2003 Sep; 86(3–5): 289–93

    Article  PubMed  CAS  Google Scholar 

  52. Buzdar A, Douma J, Davidson N, et al. Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. J Clin Oncol 2001 Jul 15; 19(14): 3357–66

    PubMed  CAS  Google Scholar 

  53. Dombernowsky P, Smith I, Falkson G, 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: 453–61

    PubMed  CAS  Google Scholar 

  54. Rose C, Vtoraya O, Pluzanska A, et al. An open randomised trial of second-line endocrine therapy in advanced breast cancer: comparison of the aromatase inhibitors letrozole and anastrozole. Eur J Cancer 2003 Nov; 39(16): 2318–27

    Article  PubMed  CAS  Google Scholar 

  55. Gershanovich M, Chaudri HA, Campos D, et al. Letrozole, a new oral aromatase inhibitor: randomised trial comparing 2.5 mg daily, 0.5 mg daily and aminoglutethimide in postmenopausal women with advanced breast cancer. Ann Oncol 1998; (9): 639–45

  56. Tominaga T, Adachi I, Sasaki Y, et al. Double-blind randomised trial comparing the non-steroidal aromatase inhibitors letrozole and fadrozole in postmenopausal women with advanced breast cancer. Ann Oncol 2003 Jan; 14(1): 62–70

    Article  PubMed  CAS  Google Scholar 

  57. Chaudri HA, Trunet PF. Letrozole: updated duration of response [letter]. J Clin Oncol 1999; 17: 3859–60

    Google Scholar 

  58. Cocquyt V, Moeremans K, Annemans L, et al. Long-term medical costs of postmenopausal breast cancer therapy. Ann Oncol 2003 Jul; 14(7): 1057–63

    Article  PubMed  CAS  Google Scholar 

  59. Dranitsaris G, Verma S, Trudeau M. Cost utility analysis of first-line hormonal therapy in advanced breast cancer: comparison of two aromatase inhibitors to tamoxifen. Am J Clin Oncol 2003 Jun; 26(3): 289–96

    PubMed  Google Scholar 

  60. Dranitsaris G, Rayson D. A cost benefit analysis of first line letrozole in hormone sensitive advanced breast cancer using time to chemotherapy as a measure of benefit [abstract no. 649]. 26th Annual San Antonio Breast Cancer Symposium; 2003 Dec 3–6; San Antonio

  61. Karnon J, Johnston SR, Jones T, et al. A trial-based cost-effectiveness analysis of letrozole followed by tamoxifen versus tamoxifen followed by letrozole for postmenopausal advanced breast cancer. Ann Oncol 2003 Nov; 14(11): 1629–33

    Article  PubMed  CAS  Google Scholar 

  62. Karnon J, Jones T. A stochastic economic evaluation of letrozole versus tamoxifen as a first-line hormonal therapy: for advanced breast cancer in postmenopausal patients. Pharmacoeconomics 2003; 21(7): 513–25

    Article  PubMed  CAS  Google Scholar 

  63. Irish W, Sherrill E, Gard C, et al. Quality-adjusted survival of letrozole versus tamoxifen in post-menopausal women with advanced breast cancer [abstract no. 258]. 25th Annual San Antonio Breast Cancer Symposium; 2002 Dec 11–14; San Antonio

  64. Fricke FU, Quednau K, Pirk O. A stochastic economic evaluation of letrozole versus tamoxifen as a first-line hormonal therapy for advanced breast cancer in postmenopausal patients in Germany. Value Health 2002 Nov-2002 31; 5: 443 plus oral presentation

    Article  Google Scholar 

  65. Delea T, Smith R, Karnon J. Cost-effectiveness of letrozole vs tamoxifen as 1st line hormonal therapy for postmenopausal women with advanced breast cancer: the US perspective [abstract no. 542]. 25th Annual San Antonio Breast Cancer Symposium; 2002 Dec 11–14; San Antonio

  66. Verma S, Rocchi A. Economic evaluation of antiaromatase agents in the second-line treatment of metastatic breast cancer. Support Care Cancer 2003 Nov; 11(11): 728–34

    Article  PubMed  Google Scholar 

  67. Nuijten M, McCormick J, Waibel F, et al. Economic evaluation of letrozole in the treatment of advanced breast cancer in postmenopausal women in Canada. Value Health 2000; 3(1): 31–9

    Article  PubMed  CAS  Google Scholar 

  68. Nuijten M, Meester L, Waibel F, et al. Cost effectiveness of letrozole in the treatment of advanced breast cancer in postmenopausal women in the UK. Pharmacoeconomics 1999; 16(4): 379–91

    Article  PubMed  CAS  Google Scholar 

  69. Leung PP, Dranitsaris G, Mather J, et al. Cost utility analysis of second line hormonal therapy in advanced breast cancer: a comparison of two aromatse inhibitors to megestrol acetate (Megace) [abstract no. 1755]. 36th Proc Am Soc Clin Oncol 2000 May 20; 19: 447

    Google Scholar 

  70. Dranitsaris G, Leung P, Mather J, et al. Cost-utility analysis of second-line hormonal therapy in advanced breast cancer: a comparison of two aromatase inhibitors to megestrol acetate. Anticancer Drugs 2000; 11: 591–601

    Article  PubMed  CAS  Google Scholar 

  71. Dranitsaris G, Verma S, Trudeau M. Cost utility analysis of first line hormonal therapy in advanced breast cancer: a comparison of two aromatase inhibitors to tamoxifen [poster]. 24th Annual San Antonio Breast Cancer Symposium; 2001 Dec 10–13 Dec; San Antonio

  72. Karnon J, Johnson SR, Jones T. Cost-effectiveness analysis of letrozole vs tamoxifen as 1st line hormonal therapy for advanced breast cancer in postmenopausal women: UK perspective [abstract no. 543]. 25th Annual San Antonio Breast Cancer Symposium; 2002 Dec 11–14; San Antonio

  73. Bonneterre J, Thürlimann B, Robertson JFR, et al. Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study. J Clin Oncol 2000 Nov 15; 18(22): 3748–57

    PubMed  CAS  Google Scholar 

  74. 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 Nov 15; 18(22): 3758–67

    PubMed  CAS  Google Scholar 

  75. Buzdar AU, Jonat W, Howell A, et al. 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 Sep 15; 83(6): 1142–52

    Article  PubMed  CAS  Google Scholar 

  76. 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 Apr; 18(7): 1399–411

    PubMed  CAS  Google Scholar 

  77. 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(2): 208–13

    Article  PubMed  CAS  Google Scholar 

  78. Jonat W, Howell A, Blomqvist C, et al. A randomised 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 1996; 32(3): 404–12

    Article  Google Scholar 

  79. Buzdar AU, Jones SE, Vogel CL, et al. A phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma. Cancer 1997 Feb 15; 79(4): 730–9

    Article  PubMed  CAS  Google Scholar 

  80. Mauskopf J, Sung J, Sendersky V, et al. Estimating the budget and health impacts of letrozole for advanced breast cancer [abstract no. PCN11 plus poster]. Value Health 2003 May–Jun; 30(6): 231–2

    Article  Google Scholar 

  81. Goldhirsch A, Wood WC, Gelber RD, et al. Meeting highlights: updated International Expert Consensus on the primary therapy of early breast cancer. J Clin Oncol 2003 Sep 1; 21(17): 3357–65

    Article  PubMed  Google Scholar 

  82. Mouridsen H, Gershanovich M. The role of aromatase inhibitors in the treatment of metastatic breast cancer. Semin Oncol 2003 Aug; 30 (4 Suppl. 14): 33–45

    Article  PubMed  CAS  Google Scholar 

  83. Buzdar AU. Endocrine therapy in the treatment of metastatic breast cancer. Semin Oncol 2001; 28: 291–304

    Article  PubMed  CAS  Google Scholar 

  84. Higa GM. New generation aromatase inhibitors in breast cancer. Pharmacoeconomics 2000 Feb; 17(2): 121–32

    Article  PubMed  CAS  Google Scholar 

  85. Nicolini A, Carpi A. Advanced breast cancer: an update and controversies on diagnosis and therapy. Biomed Pharmacother 2003; 57(10): 439–46

    Article  PubMed  CAS  Google Scholar 

  86. Mauriac L, Smith I. Aromatase inhibitors in early breast cancer treatment. Semin Oncol 2003 Aug; 30 (4 Suppl. 14): 46–57

    Article  PubMed  CAS  Google Scholar 

  87. Bonneterre J. Aromatase inhibitors as first line treatment: treatment cascade after failure of aromatase inhibitors. Breast Cancer Res Treat 2003; 81 Suppl. 1: S57–61

    Article  CAS  Google Scholar 

  88. Piccart MJ, Cardoso F, Atalay G. Letrozole’s superiority over progestins and tamoxifen challenges standards of care in endocrine therapy for metastatic breast cancer. Eur J Cancer 2002 Nov; 38 Suppl. 6: S52–4

    Article  PubMed  CAS  Google Scholar 

  89. Long BJ, Jelovac D, Handratta V, et al. Therapeutic stategies using aromatase inhibitor letrozole and tamoxifen in a breast cancer model. J Natl Cancer Inst 2004 Mar 17; 96(6): 456–65

    Article  PubMed  CAS  Google Scholar 

  90. Baum M, Buzdar AU, Cuzick J, et al. on behalf of the ATAC (Arimidex, Tamoxifen Alone or in Combination) Triallists’ Group. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 2002; 359: 2131–9

    PubMed  CAS  Google Scholar 

  91. Wong ZW, Ellis MJ. First-line endocrine treatment of breast cancer: aromatase inhibitor or antioestrogen? Br J Cancer 2004 Jan 12; 90(1): 20–5

    Article  PubMed  CAS  Google Scholar 

  92. Saphner T, Tormey DC, Gray R. Annual hazard rates of recurrence for breast cancer after primary therapy. J Clin Oncol 1996; 14(10): 2738–46

    PubMed  CAS  Google Scholar 

  93. Brenner H, Hakulinen T. Are patients diagnosed with breast cancer before age 50 years ever cured. J Clin Oncol 2004; 22(3): 432–8

    Article  PubMed  Google Scholar 

  94. Twombly R. Critics question price of success in halted clinical trial of aromatase inhibitor letrozole. J Natl Cancer Inst 2003 Dec 3; 95(23): 1738–9

    Article  PubMed  Google Scholar 

  95. Bryant J, Wolmark N. Letrozole after tamoxifen for breast cancer: what is the price of success? N Engl J Med 2003 Nov 6; 349(19): 1855–7

    Article  PubMed  CAS  Google Scholar 

  96. Buzdar AU. Letrozole in breast cancer [letter]. N Engl J Med 2004 Feb 12; 350(7): 727–30; author reply 727-30

    Article  PubMed  CAS  Google Scholar 

  97. Baum M, Buzdar A. The current status of aromatase inhibitors in the management of breast cancer. Surg Clin North Am 2003 Aug; 83(4): 973–94

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland, 1311, New Zealand

    Dene Simpson, Monique P. Curran & Caroline M. Perry

Authors
  1. Dene Simpson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Monique P. Curran
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Caroline M. Perry
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dene Simpson.

Additional information

Various sections of the manuscript reviewed by: L. Bordeleau, Medical Oncology, University of Toronto, Toronto, Ontario, Canada; H.J. Burstein, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; S.E. Come, Breast Cancer Program, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA; G.M. Higa, School of Pharmacy, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia, USA; K.I. Pritchard, Clinical Trials and Epidemiology, Toronto-Sunnybrook Regional Cancer Centre, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; C. Zielinski, Division of Oncology, Department of Medicine I, University Hospital of Vienna, Vienna, Austria.

Data Selection

Sources: Medical literature published in any language since 1980 on letrozole, identified using Medline and EMBASE, supplemented by AdisBase (a proprietary database of Adis International). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: Medline search terms were ‘letrozole’ or ‘CGS-20267’ and ‘breast cancer’ or breast neoplasms’. EMBASE search terms were ‘letrozole’ and ‘breast cancer’. AdisBase search terms were ‘letrozole’ or ‘CGS-20267’ and ‘breast-cancer’. Searches were last updated 27 April 2004.

Selection: Studies in patients with breast cancer who received letrozole. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Letrozole, breast cancer, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Simpson, D., Curran, M.P. & Perry, C.M. Letrozole. Drugs 64, 1213–1230 (2004). https://doi.org/10.2165/00003495-200464110-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200464110-00005

Keywords

Search

Navigation