A RANDOMIZED TRIAL COMPARING 2 DOSES OF THE NEW SELECTIVE AROMATASE INHIBITOR ANASTROZOLE (ARIMIDEX) WITH MEGESTROL-ACETATE IN POSTMENOPAUSAL PATIENTS WITH ADVANCED BREAST-CANCER

The aim of this study was to compare the efficacy and tolerability of the new aromatase inhibitor 'ARIMIDEX' (anastrozole) with megestrol ac etate in the treatment of advanced breast cancer in postmenopausal wom en. Anastrozole is a new potent and highly selective non-steroidal aro matase inhibitor. We conducted a prospective randomised trial comparin g two doses of anastrozole (1 and 10 mg orally once daily) with megest rol acetate (40 mg orally four times daily) in postmenopausal patients with advanced breast cancer who progressed after prior tamoxifen ther apy. All patients were analysed for efficacy as randomised (intention to treat) and for tolerability as per treatment received. Of the 378 p atients who entered the study, 135 were randomised to anastrozole 1 mg , 118 to anastrozole 10 mg, and 125 patients to megestrol acetate. Aft er a median follow-up of 192 days, response rate which included comple te response, partial response and patients who had disease stabilisati on for 6 months or more was 34% for anastrozole 1 mg, 33.9% for anastr ozole 10 mg and 32.8% for megestrol acetate. There were no statistical ly significant differences between either dose of anastrozole and mege strol acetate in terms of objective response rate, time to objective p rogression of disease or time to treatment failure. The three treatmen ts were generally well tolerated, but more patients on megestrol aceta te reported weight gain, oedema and dyspnoea as adverse events while m ore patients on anastrozole reported gastro-intestinal disorders, usua lly in the form of mild transient nausea. Patients on anastrozole did not report higher incidences of oestrogen withdrawal symptoms. Anastro zole is an effective and well tolerated treatment for postmenopausal p atients with advanced breast cancer. The higher 10 mg dose did not res ult in additional clinical benefit, but was well tolerated reflecting the good therapeutic margin with anastrozole. Based on this data, anas trozole 1 mg should be the recommended therapeutic dose.