The extended adjuvant NCIC CTG MA.17 trials: initial and rerandomization studies.
Based upon the results of the NCIC CTG MA.17 trial, letrozole has become the only approved aromatase inhibitor (AI) in the extended adjuvant treatment setting following 5 years of tamoxifen therapy. In this trial, the AI letrozole decreased the overall risk of breast cancer recurrence by 42% compared with placebo in postmenopausal women completing 5 years of tamoxifen. The benefit of letrozole exceeded the expected difference after median follow-up of more than 2 years and led to the unblinding of the trial. The 30-month updated analyses found a 4.8%, 4-year disease-free survival improvement overall, an improvement in distant disease-free recurrence in both node-negative and node-positive patients, and a survival benefit for node-positive patients. Generally well tolerated, letrozole caused some adverse events including arthralgias and osteoporosis. However, results from the Zometa-Femara adjuvant synergy trial (Z-FAST) suggest that zoledronic acid, when used concomitantly with letrozole, is able to manage bone loss in postmenopausal women with early breast cancer.
Pritchard
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KI
Division of Clinical Trials and Epidemiology, Toronto-Sunnybrook Regional Cancer Center, 2075 Bayview Avenue, North York, Ont., Canada M4N 3M5. kathy.pritchard@sw.ca
Goss
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PE
Shepherd
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L
D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077289:Letrozole; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use*; D009864:Ontario; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*
D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole