Droloxifene, a new anti-oestrogen in postmenopausal advanced breast cancer: preliminary results of a double-blind dose-finding phase II trial.

Droloxifene (3-OH-tamoxifen citrate) is a novel anti-oestrogen with a higher affinity for oestrogen receptors (ER), a lower oestrogenic to anti-oestrogenic activity ratio and faster pharmacokinetics compared with tamoxifen. From May 1988 to April 1991, 369 postmenopausal women with metastatic or locally unresectable breast cancer of which the ER or progesterone receptor status was positive or unknown, were randomised to receive an oral dose of 20, 40 or 100 mg droloxifene once daily. 43 Brazilian, Canadian and European centres took part in this double-blind phase II trial. 60 women were ineligible for violation of entry criteria; 20 were inevaluable and 15 still await definitive response evaluation. 234 patients have been evaluated for response. The over-all objective response rate (complete plus partial) was 92/234 (39.3%): 23/74 (31.1%) for 20 mg, 33/74 (44.6%) for 40 mg and 36/86 (41.9%) for 100 mg (not significantly different within this dose range). There was no significant difference in time to tumour progression between the three doses. Toxicity was minimal at all doses. These preliminary results show that droloxifene is active against advanced breast cancer. Because of its outstanding preclinical characteristics, the drug warrants large-scale clinical investigation.

RCT Entities:   Population Interventions Outcomes