Letrozole versus tamoxifen in the treatment of advanced breast cancer and as neoadjuvant therapy.
Letrozole, a third generation aromatase inhibitor, has been compared with tamoxifen in the treatment of advanced breast cancer and as neoadjuvant therapy. In a first-line trial in advanced disease, 939 post menopausal women were randomised double blind to receive treatment with letrozole 2.5 mg daily or tamoxifen 20 mg daily. Letrozole was significantly superior in terms of median time to progression (9.4 months versus 6.1 months, P=0.0001), objective response (30% versus 20%, P=0.0006), and clinical benefit (49% versus 38%, P=0.0001). Superiority of letrozole was independent of disease site, receptor status, or prior adjuvant anti-oestrogen therapy. In an extended phase of this trial, 200 patients were crossed over to tamoxifen after letrozole, compared with 197 crossed over to letrozole after tamoxifen. Median overall survival was 34 months for letrozole versus 30 months for tamoxifen (not significant). In a similar randomised double-blind neoadjuvant trial, 337 post menopausal patients with large ER/or PgR positive T2-T4 cancers, either requiring mastectomy or locally advanced, were randomised to preoperative letrozole or tamoxifen for 4 months prior to surgery. Overall response was 55% for letrozole versus 36% for tamoxifen (P<0.001). Conservative surgery was possible in 45% of patients treated with letrozole versus 35% with tamoxifen (P=0.022). In both trials, both treatments were well tolerated with no significant differences in side effects. These results indicate that letrozole is more active than tamoxifen both as neoadjuvant therapy and as first-line treatment in advanced disease. They support the importance of current adjuvant trials comparing the two treatments.
Smith
Ian E
IE
Breast Unit, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK. ian.smith@rmh.nthames.nhs.uk
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009570:Nitriles / Q000627:therapeutic use*; D017698:Postmenopause; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole