Effects of high dose raloxifene in selected patients with advanced breast carcinoma

BACKGROUND. An earlier trial of raloxifene, conducted in women with metasta tic breast carcinoma who initially had responded to tamoxifen and subsequen tly developed disease progression, suggested no antitumor activity for ralo xifene in tamoxifen-refractory disease. However, preclinical studies and pr eliminary clinical data in healthy women suggest that raloxifene antagonize s growth of estrogen-dependent neoplasia. METHODS. Raloxifene HCl 150 mg twice daily was given to 22 postmenopausal w omen with metastatic (American Joint Committee on Cancer Stage IV) or locor egionally recurrent, initially estrogen receptor positive breast carcinoma. Prior systemic treatment of metastatic disease nas not allowed. Prior adju vant chemotherapy or hormonal therapy was required to have been completed a t least 1 year before study entry. Tumor response was evaluated every other month either radiographically or by physical examination. Evaluable diseas e was defined as bidimensionally measurable lesions. RESULTS. Twenty-one patients were eligible for efficacy analysis; 6 had bee n treated previously with tamoxifen. There were no complete tumor responses . Four patients (19%; 95% confidence interval [95% CI], 2.2%, 36%) had part ial tumor responses lasting 6.3, 17.5, 23.9, and 28.1 months, respectively. Prolonged stable disease (i.e., tumor size stable for greater than or equa l to 6 months) was observed in 3 patients (14%; 95% CI, 0.0%, 29%) and last ed 7.9, 12.2, and 25.1 months, respectively Combining partial responses and prolonged stable disease yielded an overall clinical benefit rate of 33% ( 95% CI, 13%, 53%). Adverse events generally were consistent with the diseas e state; there were no serious adverse events or laboratory changes believe d to be therapy-related. CONCLUSIONS. Raloxifene HCl, 150 mg, administered twice daily was safe, wel l tolerated, and modestly effective in highly selected postmenopausal women with advanced breast carcinoma. Further study of high dose raloxifene as m onotherapy for advanced breast carcinoma most likely is unwarranted. (C) 20 00 American Cancer Society.