DROLOXIFENE IN POSTMENOPAUSAL PATIENTS WI TH METASTATIC BREAST-CANCER- DOUBLE-BLIND RANDOMIZED PHASE-II STUDY

Droloxifene (3-OH-tamoxifen) is a new, highly effective antiestrogen. In preclinical and early clinical trials a strong antineoplastic effic acy was stated, at least as effective as that of tamoxifen. The ration ale of the trial was the definition of the optimal daily dose. The tri al was double-blind randomized and included in total 369 female breast cancer patients with advanced disease. The interim analysis included 234 fully evaluable patients. The objective remission rates were 31% ( 20 mg/day), 45% (40 mg/day) and 42% (100 mg/day). There was a trend fo r higher remission rates in the 40- and 100-mg groups. However, this w as not statistically significant (p = 0.0528). The remissions were not iced very early. The medians for subjective response (pain) and object ive response (CR/PR) were noted after 2 and 8 weeks, respectively. The median time to progression was 6 months (20 and 100 mg/day) and 8.3 m onths (40 mg/day). The course of tumor markers demonstrated the rapid onset of the action of droloxifene. Droloxifene was well tolerated in all three dosages. As clinically relevant side effects, hot flushes an d nausea were noticed. A clinically irrelevant and transient increase in the gamma GT level was noticed during the first 2 weeks of treatmen t. The recommended daily dose for phase III trials is 40 mg.