title: Letrozole: a review of its use in postmenopausal women with breast cancer.
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.
authors.affiliation: Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
authors.forename: Dene
authors.initials: D
authors.lastname: Simpson
authors.forename: Monique P
authors.initials: MP
authors.lastname: Curran
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Perry
mesh_terms: D000970:Antineoplastic Agents / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D047072:Aromatase Inhibitors; D001682:Biological Availability; D001943:Breast Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000473:pathology; D003362:Cost-Benefit Analysis; D004361:Drug Tolerance; D017850:Economics, Pharmaceutical; D004791:Enzyme Inhibitors / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use; D017698:Postmenopause; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D014230:Triazoles / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole