A randomised phase III cross-over study of tamoxifen versus megestrol acetate in advanced and recurrent breast cancer

139 peri- and postmenopausal women with advanced or recurrent breast cancer who had not received prior hormonal therapy were randomised in an open, cross-over study comparing the synthetic progestogen megestrol acetate with tamoxifen. The response rate (CR/PR) to megestrol acetate (25%; 95% confidence interval (CI) 15–35%) was not significantly different from that produced by tamoxifen (33%, CI 22–44%). Time-to-treatment failure was also similar in the two groups. Cross-over treatment was given on progression in 76 cases. Cross-over response (CR/PR) was seen in 3 of 35 patients (9%) receiving megestrol acetate as second-line therapy and in 6 of 41 patients (15%) receiving tamoxifen second-line. There was no significant difference in survival between the groups (P = 0.17) with median survival times of 24 and 32 months for the megestrol acetate and tamoxifen groups, respectively. The toxicity profile of the two drugs was different, although significant toxicity was rare with either agent. Megestrol acetate is an effective treatment for advanced breast cancer in older women when used either as first- or second-line treatment. Cross-over response is seen following both treatments. Given that most patients now receive tamoxifen as adjuvant treatment, megestrol acetate would appear to be one of the logical choices for patients who find the side-effects of tamoxifen unacceptable and for those who relapse on tamoxifen with further hormone therapy being clinically indicated.