Sequential tamoxifen and aminoglutethimide versus tamoxifen alone in the adjuvant treatment of postmenopausal breast cancer patients: Results of an Italian cooperative study

Purpose : To determine whether switching patients from tamoxifen to antiaro matase treatment would prevent some of the relapses or deaths that we assum e would occur if tamoxifen were continued. Patients and Methods: Three hundred eighty postmenopausal breast cancer pat ients receiving adjuvant tamoxifen treatment for 3 years were randomized to either continue tamoxifen for 2 more years or to switch to low-dose aminog lutethimide (250 mg daily) for 2 years. Results: At a median follow-up of 61 months (range, 5 to 94 months), 59 eve nts occurred in the tamoxifen group, and 55 occurred in the aminoglutethimi de group. More treatment failures at distant sites, such as viscera (P = .0 2), were observed in the tamoxifen group. Although no differences in diseas e-free survival between the two groups have emerged so far, a significant t rend favors aminoglutethimide in overall survival (P = .005) and breast can cer-specific survival (P = .06). Even if more patients in the antiaromatase group complained of drug-related side effects and more of them discontinue d treatment (P = .0001), the number of cardiovascular events and, in genera l, of life-threatening adverse events was higher in the tamoxifen arm. Conclusion: Switching patients from tamoxifen to aminoglutethimide treatmen t resulted in comparable event-free survival, but longer overall survival w as achieved in patients who were switched to aminoglutethimide as compared with those who continued to receive tamoxifen. Should these preliminary res ults be confirmed by larger studies with a similar design, which are now te sting the effectiveness of the new, more active, and tolerable aromatase in hibitors, sequencing tamoxifen with an aromatase inhibitor could become a p referable alternative to tamoxifen alone in early breast cancer patients. ( C) 2001 by American Society of Clinical Oncology.