Sequential tamoxifen and megestrol acetate with continuous norethisterone in postmenopausal breast cancer: a feasibility study

Combined sequential tamoxifen and megace may provide more effective therapy in breast cancer than either agent alone. In a previous study this approach had been shown to be associated with improved survival in women with advanced breast cancer when compared with tamoxifen alone but at the cost of breakthrough vaginal bleeding in about 15% of patients. If this regimen is to be tested in the adjuvant setting the incidence of bleeding will need to be reduced. Within this pilot study 20 women with stage II–IV breast cancer were treated with combined sequential tamoxifen and megace on a background of low dose (1 mg/day) continuous norethisterone, which on theoretical grounds could reduce the frequency of vaginal bleeding. Vaginal bleeding occurred in eight of 20 women, and five patients withdrew from treatment because of other toxicities (thrombophlebitis, pelvic pain, and menopausal flushing and sweats). Although this type of combined endocrine therapy has produced promising results in advanced breast cancer, it is not suitable for use in the adjuvant setting.